157 results on '"Talaverón-Rey, Marta"'
Search Results
2. UPRmt activation improves pathological alterations in cellular models of mitochondrial diseases
- Author
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Suárez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, and Sánchez-Alcázar, José A.
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- 2022
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- View/download PDF
3. Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
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Álvarez-Córdoba, Mónica, Reche-López, Diana, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Villalón-García, Irene, Povea-Cabello, Suleva, Suárez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Piñero-Pérez, Rocío, and Sánchez-Alcázar, José A.
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- 2022
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4. Polydatin and Nicotinamide Rescue the Cellular Phenotype of Mitochondrial Diseases by Mitochondrial Unfolded Protein Response (mtUPR) Activation.
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Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Pérez, Rocío, Romero Domínguez, José Manuel, Talaverón-Rey, Marta, Reche-López, Diana, Suárez-Rivero, Juan Miguel, Álvarez-Córdoba, Mónica, Romero-González, Ana, López-Cabrera, Alejandra, Oliveira, Marta Castro De, Rodríguez-Sacristan, Andrés, and Sánchez-Alcázar, José Antonio
- Subjects
MITOCHONDRIAL DNA ,MITOCHONDRIAL proteins ,DENATURATION of proteins ,UNFOLDED protein response ,NICOTINAMIDE ,ELONGATION factors (Biochemistry) - Abstract
Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Parkin-mediated mitophagy and autophagy flux disruption in cellular models of MERRF syndrome
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Villanueva-Paz, Marina, Povea-Cabello, Suleva, Villalón-García, Irene, Álvarez-Córdoba, Mónica, Suárez-Rivero, Juan M., Talaverón-Rey, Marta, Jackson, Sandra, Falcón-Moya, Rafael, Rodríguez-Moreno, Antonio, and Sánchez-Alcázar, José A.
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- 2020
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- View/download PDF
6. Mitochondrial Unfolded Protein Response (Mtupr) Activation by Polydatin and Nicotinamide Corrects Pathological Alterations in Cellular Models of Gfm1 Mutations
- Author
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Cilleros-Holgado, Paula, primary, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Romero-Domínguez, José Manuel, additional, Talaverón-Rey, Marta, additional, Reche-López, Diana, additional, Suárez-Rivero, Juan Miguel, additional, Alvárez-Córdoba, Mónica, additional, Romero-González, Ana, additional, López-Cabrera, Alejandra, additional, Castro de Oliveira, Marta, additional, Rodríguez-Sacristán, Andrés, additional, and Sánchez-Alcázar, José A., additional
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- 2024
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- View/download PDF
7. Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases
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Cilleros-Holgado, Paula, primary, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Romero-Domínguez, Jose Manuel, additional, Reche-López, Diana, additional, López-Cabrera, Alejandra, additional, Álvarez-Córdoba, Mónica, additional, Munuera-Cabeza, Manuel, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Romero-González, Ana, additional, and Sánchez-Alcázar, Jose Antonio, additional
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- 2023
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8. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies
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Piñero-Pérez, Rocío, primary, López-Cabrera, Alejandra, additional, Álvarez-Córdoba, Mónica, additional, Cilleros-Holgado, Paula, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Gómez-Fernández, David, additional, Reche-López, Diana, additional, Romero-González, Ana, additional, Romero-Domínguez, José Manuel, additional, de Pablos, Rocío M., additional, and Sánchez-Alcázar, José A., additional
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- 2023
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9. Down regulation of the expression of mitochondrial phosphopantetheinyl-proteins in pantothenate kinase-associated neurodegeneration: pathophysiological consequences and therapeutic perspectives
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Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Villalón-García, Irene, Povea-Cabello, Suleva, Suárez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Salas, Joaquín J., and Sánchez-Alcázar, José A.
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- 2021
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10. Antioxidants Prevent Iron Accumulation and Lipid Peroxidation, but Do Not Correct Autophagy Dysfunction or Mitochondrial Bioenergetics in Cellular Models of BPAN
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Suárez-Carrillo, Alejandra, primary, Álvarez-Córdoba, Mónica, additional, Romero-González, Ana, additional, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Cilleros-Holgado, Paula, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Gómez-Fernández, David, additional, Romero-Domínguez, José Manuel, additional, Munuera-Cabeza, Manuel, additional, Díaz, Antonio, additional, González-Granero, Susana, additional, García-Verdugo, José Manuel, additional, and Sánchez-Alcázar, José A., additional
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- 2023
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11. Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration
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Álvarez-Córdoba, Mónica, primary, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Cilleros-Holgado, Paula, additional, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Munuera-Cabeza, Manuel, additional, Suárez-Carrillo, Alejandra, additional, Romero-González, Ana, additional, Romero-Domínguez, Jose Manuel, additional, López-Cabrera, Alejandra, additional, Armengol, José Ángel, additional, and Sánchez-Alcázar, José Antonio, additional
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- 2023
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12. Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation
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Álvarez-Córdoba, Mónica, Fernández Khoury, Aida, Villanueva-Paz, Marina, Gómez-Navarro, Carmen, Villalón-García, Irene, Suárez-Rivero, Juan M., Povea-Cabello, Suleva, de la Mata, Mario, Cotán, David, Talaverón-Rey, Marta, Pérez-Pulido, Antonio J., Salas, Joaquín J., Pérez-Villegas, Eva Mª, Díaz-Quintana, Antonio, Armengol, José A., and Sánchez-Alcázar, José A.
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- 2019
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13. Neurodegeneration, Mitochondria, and Antibiotics
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Suárez-Rivero, Juan M., primary, López-Pérez, Juan, additional, Muela-Zarzuela, Inés, additional, Pastor-Maldonado, Carmen, additional, Cilleros-Holgado, Paula, additional, Gómez-Fernández, David, additional, Álvarez-Córdoba, Mónica, additional, Munuera-Cabeza, Manuel, additional, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Suárez-Carrillo, Alejandra, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Romero-Domínguez, José M., additional, and Sánchez-Alcázar, José Antonio, additional
- Published
- 2023
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14. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies
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Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Instituto de Salud Carlos III, Junta de Andalucía, Piñero Pérez, Rocío, López Cabrera, Alejandra, Álvarez Córdoba, Mónica, Cilleros Holgado, Paula, Talaverón Rey, Marta, Suárez Carrillo, Alejandra, Munuera Cabeza, Manuel, Gómez Fernández, David, Reche López, Diana, Romero González, Ana Belén, Romero Domínguez, José Manuel, Martínez de Pablos, Rocío, Sánchez Alcázar, José Antonio, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Instituto de Salud Carlos III, Junta de Andalucía, Piñero Pérez, Rocío, López Cabrera, Alejandra, Álvarez Córdoba, Mónica, Cilleros Holgado, Paula, Talaverón Rey, Marta, Suárez Carrillo, Alejandra, Munuera Cabeza, Manuel, Gómez Fernández, David, Reche López, Diana, Romero González, Ana Belén, Romero Domínguez, José Manuel, Martínez de Pablos, Rocío, and Sánchez Alcázar, José Antonio
- Abstract
Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of “nemaline bodies” (rods) in muscle fibers by histopathological examination. The most common forms of NM are caused by mutations in the Actin Alpha 1 (ACTA1) and Nebulin (NEB) genes. Clinical features include hypotonia and muscle weakness. Unfortunately, there is no curative treatment and the pathogenetic mechanisms remain unclear. In this manuscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine–phalloidin to analyze the polymerization of actin filaments by fluorescence microscopy. We found that patients’ fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects were associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial-boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibroblasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.
- Published
- 2023
15. mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
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Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Reche-López, Diana, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Romero-González, Ana, Suarez-Rivero, Juan M., Romero-Domínguez, José Manuel, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Reche-López, Diana, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Romero-González, Ana, Suarez-Rivero, Juan M., Romero-Domínguez, José Manuel, and Sánchez-Alcázar, José Antonio
- Abstract
Mitochondrial dysfunction is a key pathological event in many diseases. Its role in energy production, calcium homeostasis, apoptosis regulation, and reactive oxygen species (ROS) balance render mitochondria essential for cell survival and fitness. However, there are no effective treatments for most primary and secondary mitochondrial diseases to this day. Therefore, new therapeutic approaches, such as the modulation of the mitochondrial unfolded protein response (mtUPR), are being explored. mtUPRs englobe several compensatory processes related to proteostasis and antioxidant system mechanisms. mtUPR activation, through an overcompensation for mild intracellular stress, promotes cell homeostasis and improves lifespan and disease alterations in biological models of mitochondrial dysfunction in age-related diseases, cardiopathies, metabolic disorders, and primary mitochondrial diseases. Although mtUPR activation is a promising therapeutic option for many pathological conditions, its activation could promote tumor progression in cancer patients, and its overactivation could lead to non-desired side effects, such as the increased heteroplasmy of mitochondrial DNA mutations. In this review, we present the most recent data about mtUPR modulation as a therapeutic approach, its role in diseases, and its potential negative consequences in specific pathological situations.
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- 2023
16. Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases
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Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Industria, Energía y Turismo (España), Junta de Andalucía, Fundación Merck Salud, Universidad Pablo de Olavide, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Romero-Domínguez, José Manuel, Reche-López, Diana, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Romero-González, Ana, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Industria, Energía y Turismo (España), Junta de Andalucía, Fundación Merck Salud, Universidad Pablo de Olavide, Cilleros-Holgado, Paula, Gómez-Fernández, David, Piñero-Perez, Rocío, Romero-Domínguez, José Manuel, Reche-López, Diana, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Romero-González, Ana, and Sánchez-Alcázar, José Antonio
- Abstract
Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich’s Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR’s role as a promising therapeutic target in combating these devastating disorders.
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- 2023
17. Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration
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Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Villalón-García, Irene, Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Villalón-García, Irene, Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, and Sánchez-Alcázar, José Antonio
- Abstract
Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, or neurodegeneration with brain iron accumulation disorders. Mitochondrial dysfunction, lipofuscin accumulation, autophagy disruption, and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders. Currently, the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear. In this review, we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation, and the effect of iron overload on lipid peroxidation and cellular function. The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration. Therefore, the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration. In addition, we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration, particularly in PLA2G6-associated neurodegeneration, a rare neurodegenerative disease with autosomal recessive inheritance, which belongs to the group of neurodegeneration with brain iron accumulation disorders.
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- 2023
18. Actin Polymerization Defects Induce Mitochondrial Dysfunction in Cellular Models of Nemaline Myopathies
- Author
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Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Piñero-Perez, Rocío, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Gómez-Fernández, David, Reche-López, Diana, Romero-González, Ana, Romero-Domínguez, José Manuel, Pablos, Rocío M. de, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Piñero-Perez, Rocío, López-Cabrera, Alejandra, Álvarez-Córdoba, Mónica, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Gómez-Fernández, David, Reche-López, Diana, Romero-González, Ana, Romero-Domínguez, José Manuel, Pablos, Rocío M. de, and Sánchez-Alcázar, José Antonio
- Abstract
Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of “nemaline bodies” (rods) in muscle fibers by histopathological examination. The most common forms of NM are caused by mutations in the Actin Alpha 1 (ACTA1) and Nebulin (NEB) genes. Clinical features include hypotonia and muscle weakness. Unfortunately, there is no curative treatment and the pathogenetic mechanisms remain unclear. In this manuscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine–phalloidin to analyze the polymerization of actin filaments by fluorescence microscopy. We found that patients’ fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects were associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial-boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibroblasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.
- Published
- 2023
19. Neurodegeneration, Mitochondria, and Antibiotics
- Author
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Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía, Industria y Competitividad (España), Ministerio de Universidades (España), Junta de Andalucía, Suarez-Rivero, Juan M., López-Pérez, Juan, Muela-Zarzuela, Inés, Pastor-Maldonado, Carmen J., Cilleros-Holgado, Paula, Gómez-Fernández, David, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Piñero-Perez, Rocío, Reche-López, Diana, Romero-Domínguez, José Manuel, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía, Industria y Competitividad (España), Ministerio de Universidades (España), Junta de Andalucía, Suarez-Rivero, Juan M., López-Pérez, Juan, Muela-Zarzuela, Inés, Pastor-Maldonado, Carmen J., Cilleros-Holgado, Paula, Gómez-Fernández, David, Álvarez-Córdoba, Mónica, Munuera, Manuel, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suárez-Carrillo, Alejandra, Piñero-Perez, Rocío, Reche-López, Diana, Romero-Domínguez, José Manuel, and Sánchez-Alcázar, José Antonio
- Abstract
Neurodegenerative diseases are characterized by the progressive loss of neurons, synapses, dendrites, and myelin in the central and/or peripheral nervous system. Actual therapeutic options for patients are scarce and merely palliative. Although they affect millions of patients worldwide, the molecular mechanisms underlying these conditions remain unclear. Mitochondrial dysfunction is generally found in neurodegenerative diseases and is believed to be involved in the pathomechanisms of these disorders. Therefore, therapies aiming to improve mitochondrial function are promising approaches for neurodegeneration. Although mitochondrial-targeted treatments are limited, new research findings have unraveled the therapeutic potential of several groups of antibiotics. These drugs possess pleiotropic effects beyond their anti-microbial activity, such as anti-inflammatory or mitochondrial enhancer function. In this review, we will discuss the controversial use of antibiotics as potential therapies in neurodegenerative diseases.
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- 2023
20. mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases
- Author
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Cilleros-Holgado, Paula, primary, Gómez-Fernández, David, additional, Piñero-Pérez, Rocío, additional, Reche-López, Diana, additional, Álvarez-Córdoba, Mónica, additional, Munuera-Cabeza, Manuel, additional, Talaverón-Rey, Marta, additional, Povea-Cabello, Suleva, additional, Suárez-Carrillo, Alejandra, additional, Romero-González, Ana, additional, Suárez-Rivero, Juan Miguel, additional, Romero-Domínguez, Jose Manuel, additional, and Sánchez-Alcázar, Jose Antonio, additional
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- 2023
- Full Text
- View/download PDF
21. Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration
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Sánchez-Alcázar, JoséA, primary, Villalón-García, Irene, additional, Povea-Cabello, Suleva, additional, Álvarez-Córdoba, Mónica, additional, Talaverón-Rey, Marta, additional, Suárez-Rivero, JuanM, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Reche-López, Diana, additional, Cilleros-Holgado, Paula, additional, and Piñero-Pérez, Rocío, additional
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- 2023
- Full Text
- View/download PDF
22. Pantothenate and L-Carnitine Supplementation Improves Pathological Alterations in Cellular Models of KAT6A Syndrome
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Munuera-Cabeza, Manuel, primary, Álvarez-Córdoba, Mónica, additional, Suárez-Rivero, Juan M., additional, Povea-Cabello, Suleva, additional, Villalón-García, Irene, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Reche-López, Diana, additional, Cilleros-Holgado, Paula, additional, Piñero-Pérez, Rocío, additional, and Sánchez-Alcázar, José A., additional
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- 2022
- Full Text
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23. Alpha-Lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
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Talaverón-Rey, Marta, primary, Álvarez-Córdoba, Mónica, additional, Villalón-García, Irene, additional, Povea-Cabello, Suleva, additional, Suárez-Rivero, Juan M., additional, Gómez-Fernández, David, additional, Romero-González, Ana, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Cilleros-Holgado, Paula, additional, Reche-López, Diana, additional, Piñero-Pérez, Rocío, additional, and Alcazar, Jose A Sanchez, additional
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- 2022
- Full Text
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24. Pantothenate and L-carnitine Supplementation Corrects Pathological Alterations in Cellular Models of KAT6A Syndrome
- Author
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Munuera-Cabeza, Manuel, primary, Álvarez-Córdoba, Mónica, additional, Suárez-Rivero, Juan M., additional, Povea-Cabello, Suleva, additional, Villalón-García, Irene, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Reche-López, Diana, additional, Cilleros-Holgado, Paula, additional, Piñero-Pérez, Rocío, additional, and Sánchez-Alcázar, José A., additional
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- 2022
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25. Additional file 1 of Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
- Author
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Talaverón-Rey, Marta, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Povea-Cabello, Suleva, Suárez-Rivero, Juan M., Gómez-Fernández, David, Romero-González, Ana, Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Cilleros-Holgado, Paula, Reche-López, Diana, Piñero-Pérez, Rocío, and Sánchez-Alcázar, José A.
- Abstract
Additional file 1. Supplementary figures.
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- 2023
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26. Modeling Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome Using Patient-Derived Induced Neurons Generated by Direct Reprogramming
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Povea-Cabello, Suleva, primary, Villanueva-Paz, Marina, additional, Villalón-García, Irene, additional, Talaverón-Rey, Marta, additional, Álvarez-Cordoba, Mónica, additional, Suárez-Rivero, Juan M., additional, Montes, María Ángeles, additional, Rodríguez-Moreno, Antonio, additional, Andrade-Talavera, Yuniesky, additional, Armengol, José A., additional, and Sánchez-Alcázar, José A., additional
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- 2022
- Full Text
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27. Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration.
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Villalón-García, Irene, Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Suárez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Pérez, Rocío, and Sánchez-Alcázar, José A.
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- 2023
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28. Activation of the Mitochondrial Unfolded Protein Response: A New Therapeutic Target?
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Suárez-Rivero, Juan M., primary, Pastor-Maldonado, Carmen J., additional, Povea-Cabello, Suleva, additional, Álvarez-Córdoba, Mónica, additional, Villalón-García, Irene, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Reche-López, Diana, additional, Cilleros-Holgado, Paula, additional, Piñero-Pérez, Rocío, additional, and Sánchez-Alcázar, José A., additional
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- 2022
- Full Text
- View/download PDF
29. Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels.
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Álvarez-Córdoba, Mónica, primary, Reche-López, Diana, additional, Cilleros-Holgado, Paula, additional, Talaverón-Rey, Marta, additional, Villalón-García, Irene, additional, Povea-Cabello, Suleva, additional, Suárez-Rivero, Juan M, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Piñero-Pérez, Rocío, additional, and Alcazar, Jose A Sanchez, additional
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- 2022
- Full Text
- View/download PDF
30. Modeling mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome using patient-derived induced neurons generated by direct reprogramming
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Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Instituto de Salud Carlos III, Povea-Cabello, Suleva, Villanueva-Paz, Marina, Villalón-García, Irene, Talaverón-Rey, Marta, Álvarez-Córdoba, Mónica, Suarez-Rivero, Juan M., Montes, María Ángeles, Rodríguez-Moreno, Antonio, Andrade-Talavera, Yuniesky, Armengol, José Ángel, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Instituto de Salud Carlos III, Povea-Cabello, Suleva, Villanueva-Paz, Marina, Villalón-García, Irene, Talaverón-Rey, Marta, Álvarez-Córdoba, Mónica, Suarez-Rivero, Juan M., Montes, María Ángeles, Rodríguez-Moreno, Antonio, Andrade-Talavera, Yuniesky, Armengol, José Ángel, and Sánchez-Alcázar, José Antonio
- Abstract
Mitochondrial diseases are a heterogeneous group of rare genetic disorders caused by mutations in nuclear or mitochondrial DNA (mtDNA). These diseases are frequently multisystemic, although mainly affect tissues that require large amounts of energy such as the brain. Mutations in mitochondrial transfer RNA (mt-tRNA) lead to defects in protein translation that may compromise some or all mtDNA-encoded proteins. Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS) syndrome is mainly caused by the m.3243A>G mutation in the mt-tRNALeu(UUR) (MT-TL1) gene. Owing to the lack of proper animal models, several cellular models have been developed to study the disease, providing insight in the pathophysiological mechanisms of MELAS. In this study, we show a successful direct conversion of MELAS patient-derived fibroblasts into induced neurons (iNs) for the first time, as well as an electrophysiological characterization of iNs cocultured with astrocytes. In addition, we performed bioenergetics analysis to study the consequences of m.3243A>G mutation in this neuronal model of MELAS syndrome.
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- 2022
31. Activation of the mitochondrial unfolded protein response: A new therapeutic target?
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Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, and Sánchez-Alcázar, José Antonio
- Abstract
Mitochondrial dysfunction is a key hub that is common to many diseases. Mitochondria’s role in energy production, calcium homeostasis, and ROS balance makes them essential for cell survival and fitness. However, there are no effective treatments for most mitochondrial and related diseases to this day. Therefore, new therapeutic approaches, such as activation of the mitochondrial unfolded protein response (UPRmt), are being examined. UPRmt englobes several compensation processes related to proteostasis and antioxidant mechanisms. UPRmt activation, through an hormetic response, promotes cell homeostasis and improves lifespan and disease conditions in biological models of neurodegenerative diseases, cardiopathies, and mitochondrial diseases. Although UPRmt activation is a promising therapeutic option for many conditions, its overactivation could lead to non-desired side effects, such as increased heteroplasmy of mitochondrial DNA mutations or cancer progression in oncologic patients. In this review, we present the most recent UPRmt activation therapeutic strategies, UPRmt’s role in diseases, and its possible negative consequences in particular pathological conditions.
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- 2022
32. Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
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Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Álvarez-Córdoba, Mónica, Reche-López, Diana, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Villalón-García, Irene, Povea-Cabello, Suleva, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Piñero-Perez, Rocío, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Álvarez-Córdoba, Mónica, Reche-López, Diana, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Villalón-García, Irene, Povea-Cabello, Suleva, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Piñero-Perez, Rocío, and Sánchez-Alcázar, José Antonio
- Abstract
[Background]: Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA subtypes. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) that result in dysfunction in PANK2 enzyme activity, with consequent deficiency of coenzyme A (CoA) biosynthesis, as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine, a necessary cofactor for essential cytosolic and mitochondrial proteins. [Methods]: In this manuscript, we examined the therapeutic effectiveness of pantothenate, panthetine, antioxidants (vitamin E and omega 3) and mitochondrial function boosting supplements (L-carnitine and thiamine) in mutant PANK2 cells with residual expression levels. [Results]: Commercial supplements, pantothenate, pantethine, vitamin E, omega 3, carnitine and thiamine were able to eliminate iron accumulation, increase PANK2, mtACP, and NFS1 expression levels and improve pathological alterations in mutant cells with residual PANK2 expression levels. [Conclusion]: Our results suggest that several commercial compounds are indeed able to significantly correct the mutant phenotype in cellular models of PKAN. These compounds alone or in combinations are of common use in clinical practice and may be useful for the treatment of PKAN patients with residual enzyme expression levels.
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- 2022
33. Pantothenate and L-Carnitine supplementation improves pathological alterations in cellular models of KAT6A syndrome
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Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Munuera, Manuel, Álvarez-Córdoba, Mónica, Suarez-Rivero, Juan M., Povea-Cabello, Suleva, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Munuera, Manuel, Álvarez-Córdoba, Mónica, Suarez-Rivero, Juan M., Povea-Cabello, Suleva, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, and Sánchez-Alcázar, José Antonio
- Abstract
Mutations in several genes involved in the epigenetic regulation of gene expression have been considered risk alterations to different intellectual disability (ID) syndromes associated with features of autism spectrum disorder (ASD). Among them are the pathogenic variants of the lysine-acetyltransferase 6A (KAT6A) gene, which causes KAT6A syndrome. The KAT6A enzyme participates in a wide range of critical cellular functions, such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiological alterations in fibroblasts derived from three patients harboring KAT6A mutations. We addressed survival in a stress medium, histone acetylation, protein expression patterns, and transcriptome analysis, as well as cell bioenergetics. In addition, we evaluated the therapeutic effectiveness of epigenetic modulators and mitochondrial boosting agents, such as pantothenate and L-carnitine, in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and partially corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, the cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly improve the mutant phenotype in cellular models of KAT6A syndrome.
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- 2022
34. Pterostilbene in combination with mitochondrial cofactors improve mitochondrial function in cellular models of mitochondrial diseases
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Ministerio de Sanidad (España), European Commission, Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Romero-González, Ana, Gómez-Fernández, David, Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Ministerio de Sanidad (España), European Commission, Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Romero-González, Ana, Gómez-Fernández, David, Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, and Suárez-Carrillo, Alejandra
- Abstract
Mitochondrial diseases are genetic disorders caused by mutations in genes in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) that encode mitochondrial structural or functional proteins. Although considered “rare” due to their low incidence, such diseases affect thousands of patients’ lives worldwide. Despite intensive research efforts, most mitochondrial diseases are still incurable. Recent studies have proposed the modulation of cellular compensatory pathways such as mitophagy, AMP-activated protein kinase (AMPK) activation or the mitochondrial unfolded protein response (UPRmt) as novel therapeutic approaches for the treatment of these pathologies. UPRmt is an intracellular compensatory pathway that signals mitochondrial stress to the nucleus for the activation of mitochondrial proteostasis mechanisms including chaperones, proteases and antioxidants. In this work a potentially beneficial molecule, pterostilbene (a resveratrol analogue), was identified as mitochondrial booster in drug screenings. The positive effects of pterostilbene were significantly increased in combination with a mitochondrial cocktail (CoC3) consisting of: pterostilbene, nicotinamide, riboflavin, thiamine, biotin, lipoic acid and l-carnitine. CoC3 increases sirtuins’ activity and UPRmt activation, thus improving pathological alterations in mutant fibroblasts and induced neurons.
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- 2022
35. UPRmt activation improves pathological alterations in cellular models of mitochondrial diseases
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Ministerio de Sanidad (España), European Commission, Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Junta de Andalucía, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, and Sánchez-Alcázar, José Antonio
- Abstract
Background: Mitochondrial diseases represent one of the most common groups of genetic diseases. With a prevalence greater than 1 in 5000 adults, such diseases still lack effective treatment. Current therapies are purely palliative and, in most cases, insufficient. Novel approaches to compensate and, if possible, revert mitochondrial dysfunction must be developed. Results: In this study, we tackled the issue using as a model fibroblasts from a patient bearing a mutation in the GFM1 gene, which is involved in mitochondrial protein synthesis. Mutant GFM1 fibroblasts could not survive in galactose restrictive medium for more than 3 days, making them the perfect screening platform to test several compounds. Tetracycline enabled mutant GFM1 fibroblasts survival under nutritional stress. Here we demonstrate that tetracycline upregulates the mitochondrial Unfolded Protein Response (UPR), a compensatory pathway regulating mitochondrial proteostasis. We additionally report that activation of UPR improves mutant GFM1 cellular bioenergetics and partially restores mitochondrial protein expression. Conclusions: Overall, we provide compelling evidence to propose the activation of intrinsic cellular compensatory mechanisms as promising therapeutic strategy for mitochondrial diseases.
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- 2022
36. Vitamin E prevents lipid peroxidation and iron accumulation in PLA2G6-Associated Neurodegeneration
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Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Association Internationale de Dystrophie Neuro Axonale Infantile, Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España), Asociación de Enfermos de Patologías Mitocondriales (España), Fundación MERK Salud, Villalón-García, Irene, Álvarez-Córdoba, Mónica, Povea-Cabello, Suleva, Talaverón-Rey, Marta, Villanueva-Paz, Marina, Luzón-Hidalgo, Raquel, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Salas, Joaquín J., Falcón-Moya, Rafael, Rodríguez-Moreno, Antonio, Armengol, José A., Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Association Internationale de Dystrophie Neuro Axonale Infantile, Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España), Asociación de Enfermos de Patologías Mitocondriales (España), Fundación MERK Salud, Villalón-García, Irene, Álvarez-Córdoba, Mónica, Povea-Cabello, Suleva, Talaverón-Rey, Marta, Villanueva-Paz, Marina, Luzón-Hidalgo, Raquel, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Salas, Joaquín J., Falcón-Moya, Rafael, Rodríguez-Moreno, Antonio, Armengol, José A., and Sánchez-Alcázar, José Antonio
- Abstract
PLA2G6-Associated Neurodegeneration (PLAN) is a rare neurodegenerative disease with autosomal recessive inheritance, which belongs to the NBIA (Neurodegeneration with Brain Iron Accumulation) group. Although the pathogenesis of the disease remains largely unclear, lipid peroxidation seems to play a central role in the pathogenesis. Currently, there is no cure for the disease.
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- 2022
37. Vitamin E prevents lipid peroxidation and iron accumulation in PLA2G6-Associated Neurodegeneration
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Villalón-García, Irene, primary, Álvarez-Córdoba, Mónica, additional, Povea-Cabello, Suleva, additional, Talaverón-Rey, Marta, additional, Villanueva-Paz, Marina, additional, Luzón-Hidalgo, Raquel, additional, Suárez-Rivero, Juan M., additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, Salas, Joaquín J., additional, Falcón-Moya, Rafael, additional, Rodríguez-Moreno, Antonio, additional, Armengol, José A., additional, and Sánchez-Alcázar, José A., additional
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- 2022
- Full Text
- View/download PDF
38. Pterostilbene in Combination With Mitochondrial Cofactors Improve Mitochondrial Function in Cellular Models of Mitochondrial Diseases
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Suárez-Rivero, Juan M., primary, Pastor-Maldonado, Carmen J., additional, Romero-González, Ana, additional, Gómez-Fernandez, David, additional, Povea-Cabello, Suleva, additional, Álvarez-Córdoba, Mónica, additional, Villalón-García, Irene, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, and Sánchez-Alcázar, José A., additional
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- 2022
- Full Text
- View/download PDF
39. Additional file 1 of UPRmt activation improves pathological alterations in cellular models of mitochondrial diseases
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Suárez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, and Sánchez-Alcázar, José A.
- Abstract
Additional file 1.Supplementary figures.
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- 2022
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40. UPRmt activation improves pathological alterations in cellular models of mitochondrial diseases
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Suárez-Rivero, Juan M, Pastor-Maldonado, Carmen J, Romero-González, Ana, Gómez-Fernandez, David, Suleva Povea-Cabello, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Reche-López, Diana, Cilleros-Holgado, Paula, Piñero-Perez, Rocío, and Sánchez-Alcázar, José A
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- 2022
- Full Text
- View/download PDF
41. Additional file 1 of Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels
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Álvarez-Córdoba, Mónica, Reche-López, Diana, Cilleros-Holgado, Paula, Talaverón-Rey, Marta, Villalón-García, Irene, Povea-Cabello, Suleva, Suárez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Piñero-Pérez, Rocío, and Sánchez-Alcázar, José A.
- Abstract
Additional file 1. Supplementary figures.
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- 2022
- Full Text
- View/download PDF
42. Mitochondria and Antibiotics: For Good or for Evil?
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Suárez-Rivero, Juan M., primary, Pastor-Maldonado, Carmen J., additional, Povea-Cabello, Suleva, additional, Álvarez-Córdoba, Mónica, additional, Villalón-García, Irene, additional, Talaverón-Rey, Marta, additional, Suárez-Carrillo, Alejandra, additional, Munuera-Cabeza, Manuel, additional, and Sánchez-Alcázar, José A., additional
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- 2021
- Full Text
- View/download PDF
43. Coenzyme Q10 Analogues: Benefits and Challenges for Therapeutics
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Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Munuera, Manuel, Suárez-Carrillo, Alejandra, Talaverón-Rey, Marta, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Ministerio de Ciencia e Innovación (España), Asociación de Enfermos de Patologías Mitocondriales (España), and Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España)
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Analogues ,Therapies ,Coenzyme Q10 ,Antioxidant ,Medical applications - Abstract
© 2021 by the authors. Coenzyme Q10 (CoQ10 or ubiquinone) is a mobile proton and electron carrier of the mitochondrial respiratory chain with antioxidant properties widely used as an antiaging health supplement and to relieve the symptoms of many pathological conditions associated with mitochondrial dysfunction. Even though the hegemony of CoQ10 in the context of antioxidant-based treatments is undeniable, the future primacy of this quinone is hindered by the promising features of its numerous analogues. Despite the unimpeachable performance of CoQ10 therapies, problems associated with their administration and intraorganismal delivery has led clinicians and scientists to search for alternative derivative molecules. Over the past few years, a wide variety of CoQ10 analogues with improved properties have been developed. These analogues conserve the antioxidant features of CoQ10 but present upgraded characteristics such as water solubility or enhanced mitochondrial accumulation. Moreover, recent studies have proven that some of these analogues might even outperform CoQ10 in the treatment of certain specific diseases. The aim of this review is to provide detailed information about these Coenzyme Q10 analogues, as well as their functionality and medical applications. This work was supported by FIS PI16/00786 and FIS PI19/00377 grants, Instituto de Salud Carlos III, Ministerio de Sanidad, Spain and Fondo Europeo de Desarrollo Regional (FEDER Unión Europea), Ayudas para la Formación de Profesorado Universitario (FPU), Ministerio de Ciencia e innovación; and AEPMI (Asociación de Enfermos de Patología Mitocondrial) and ENACH (Asociación de enfermos de Neurodegeneración con Acumulación Cerebral de Hierro).
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- 2021
44. Cellular models for Phospholipase A2 group VI (PLA2G6) associated neurodegeneration (PLAN) research
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Villalón-García, Irene, Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Povea-Cabello, Suleva, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, and Sánchez-Alcázar, José Antonio
- Abstract
Trabajo presentado en la International Scientific Conference on Infantile Neuroaxonal Dystrophy (INAD) and other types of PLA2G6-associated neurodegeneration (PLAN), celebrada en modalidad virtual el 30 de septiembre de 2021.
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- 2021
45. Mitochondria and antibiotics: For good or for evil?
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Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía, Industria y Competitividad (España), Junta de Andalucía, Ministerio de Economía y Competitividad (España), Asociación de Enfermos de Patologías Mitocondriales (España), Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España), Federación Española de Enfermedades Raras, Fundación Merck Salud, and Real e Ilustre Colegio de Farmacéuticos de Sevilla
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Unfolded protein response ,Aging ,Antibiotics ,Diabetes ,Mitochondrial diseases ,Obesity ,Neurodegeneration ,Mitochondria ,Cancer ,Muscle fatigue - Abstract
© 2021 by the authors. The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed. This work was supported by FIS PI16/00786 (2016) and FIS PI19/00377 (2019) grants, Ministerio de Sanidad, Spain and Fondo Europeo de Desarrollo Regional (FEDER Unión Europea), Spanish Ministry of Education, Culture and Sport. This activity has been co-financed by the European Regional Development Fund (ERDF) and by the Regional Ministry of Economic Transformation, Industry, Knowledge and Universities of the Junta de Andalucía, within the framework of the ERDF Andalusia operational program 2014–2020 Thematic objective “01—Reinforcement of research, technological develop-ment and innovation” through the reference research project CTS-5725 and PY18-850. We acknowledge the support of “Ayudas para la Formación de Profesorado Universitario” (FPU/MINECO), AEPMI (Asociación de Enfermos de Patología Mitocondrial), ENACH (Asociación de enfermos de Neurodegeneración con Acumulación Cerebral de Hierro), FEDER (Federación Española de Enfermedades Raras), Yo Nemálínica Association, KAT6A Association, Fundación MERCK Salud and Fundación MEHUER/Colegio Oficial de Farmacéuticos de Sevilla.
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- 2021
46. From Mitochondria to Atherosclerosis: The Inflammation Path
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Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), and Junta de Andalucía
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Inflammation ,NLRP3 ,Atherosclerosis ,Reactive oxygen species ,Mitochondria ,Inflammasome - Abstract
© 2021 by the authors Inflammation is a key process in metazoan organisms due to its relevance for innate defense against infections and tissue damage. However, inflammation is also implicated in pathological processes such as atherosclerosis. Atherosclerosis is a chronic inflammatory disease of the arterial wall where unstable atherosclerotic plaque rupture causing platelet aggregation and thrombosis may compromise the arterial lumen, leading to acute or chronic ischemic syndromes. In this review, we will focus on the role of mitochondria in atherosclerosis while keeping inflammation as a link. Mitochondria are the main source of cellular energy. Under stress, mitochondria are also capable of controlling inflammation through the production of reactive oxygen species (ROS) and the release of mitochondrial components, such as mitochondrial DNA (mtDNA), into the cytoplasm or into the extracellular matrix, where they act as danger signals when recognized by innate immune receptors. Primary or secondary mitochondrial dysfunctions are associated with the initiation and progression of atherosclerosis by elevating the production of ROS, altering mitochondrial dynamics and energy supply, as well as promoting inflammation. Knowing and understanding the pathways behind mitochondrial-based inflammation in atheroma progression is essential to discovering alternative or complementary treatments. This work was supported by the FIS PI16/00786 (2016) and FIS PI19/00377 (2019), Instituto de Salud Carlos III, Ministerio de Sanidad, Spain, and Fondo Europeo de Desarrollo Regional (FEDER Unión Europea), Spanish Ministry of Education, Culture and Sport, Spain. This activity has been co-financed by the European Regional Development Fund (ERDF) and by the Regional Ministry of Economic Transformation, Industry, Knowledge and Universities of the Junta de Andalucía, within the framework of the ERDF Andalusia operational program 2014–2020 thematic objective “01—Reinforcement of research, technological development and innovation” through the reference research projects CTS-5725 and PY18-850.
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- 2021
47. Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients' Brain in a Dish
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Povea-Cabello, Suleva, Villanueva-Paz, Marina, Suarez-Rivero, Juan M., Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), and Asociación de Enfermos de Patologías Mitocondriales (España)
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Disease modeling ,Direct reprogramming ,mtDNA ,Induced neurons ,Mitochondrial diseases - Abstract
© 2021 Povea-Cabello, Villanueva-Paz, Suárez-Rivero, Álvarez-Córdoba, Villalón-García, Talaverón-Rey, Suárez-Carrillo, Munuera-Cabeza and Sánchez-Alcázar. Mitochondrial diseases are a heterogeneous group of rare genetic disorders that can be caused by mutations in nuclear (nDNA) or mitochondrial DNA (mtDNA). Mutations in mtDNA are associated with several maternally inherited genetic diseases, with mitochondrial dysfunction as a main pathological feature. These diseases, although frequently multisystemic, mainly affect organs that require large amounts of energy such as the brain and the skeletal muscle. In contrast to the difficulty of obtaining neuronal and muscle cell models, the development of induced pluripotent stem cells (iPSCs) has shed light on the study of mitochondrial diseases. However, it is still a challenge to obtain an appropriate cellular model in order to find new therapeutic options for people suffering from these diseases. In this review, we deepen the knowledge in the current models for the most studied mt-tRNA mutation-caused mitochondrial diseases, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonic epilepsy with ragged red fibers) syndromes, and their therapeutic management. In particular, we will discuss the development of a novel model for mitochondrial disease research that consists of induced neurons (iNs) generated by direct reprogramming of fibroblasts derived from patients suffering from MERRF syndrome. We hypothesize that iNs will be helpful for mitochondrial disease modeling, since they could mimic patient’s neuron pathophysiology and give us the opportunity to correct the alterations in one of the most affected cellular types in these disorders. This work was supported by PI19/00377 grant, Instituto de Salud Carlos III, Spain, and Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), Spanish Ministry of Education, Culture and Sport, “Ayudas para la Formación de Profesorado Universitario” (FPU), and AEPMI (Asociación de Enfermos de Patología Mitocondrial).
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- 2021
48. Additional file 1 of Down regulation of the expression of mitochondrial phosphopantetheinyl-proteins in pantothenate kinase-associated neurodegeneration: pathophysiological consequences and therapeutic perspectives
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Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Villalón-García, Irene, Suleva Povea-Cabello, Suárez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera-Cabeza, Manuel, Salas, Joaquín J., and Sánchez-Alcázar, José A.
- Abstract
Additional file 1. Direct reprograming: neuronal conversion efficiency and neuronal purity.
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- 2021
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49. Mitochondria and antibiotics: For good or for evil?
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Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía, Industria y Competitividad (España), Junta de Andalucía, Ministerio de Economía y Competitividad (España), Asociación de Enfermos de Patologías Mitocondriales (España), Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España), Federación Española de Enfermedades Raras, Fundación Merck Salud, Real e Ilustre Colegio de Farmacéuticos de Sevilla, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, Sánchez-Alcázar, José Antonio, Ministerio de Sanidad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Ministerio de Economía, Industria y Competitividad (España), Junta de Andalucía, Ministerio de Economía y Competitividad (España), Asociación de Enfermos de Patologías Mitocondriales (España), Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España), Federación Española de Enfermedades Raras, Fundación Merck Salud, Real e Ilustre Colegio de Farmacéuticos de Sevilla, Suarez-Rivero, Juan M., Pastor-Maldonado, Carmen J., Povea-Cabello, Suleva, Álvarez-Córdoba, Mónica, Villalón-García, Irene, Talaverón-Rey, Marta, Suárez-Carrillo, Alejandra, Munuera, Manuel, and Sánchez-Alcázar, José Antonio
- Abstract
The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed.
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- 2021
50. Down regulation of the expression of mitochondrial phosphopantetheinyl-proteins in pantothenate kinase-associated neurodegeneration: pathophysiological consequences and therapeutic perspectives
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Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España), Asociación de Enfermos de Patologías Mitocondriales (España), Federación Española de Enfermedades Raras, Fundación Merck Salud, Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Villalón-García, Irene, Povea-Cabello, Suleva, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Salas, Joaquín J., Sánchez-Alcázar, José Antonio, Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro (España), Asociación de Enfermos de Patologías Mitocondriales (España), Federación Española de Enfermedades Raras, Fundación Merck Salud, Álvarez-Córdoba, Mónica, Talaverón-Rey, Marta, Villalón-García, Irene, Povea-Cabello, Suleva, Suarez-Rivero, Juan M., Suárez-Carrillo, Alejandra, Munuera, Manuel, Salas, Joaquín J., and Sánchez-Alcázar, José Antonio
- Abstract
Background: Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4'-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes. Methods: In this manuscript, we examined the effect of PANK2 mutations on the expression levels of proteins with phosphopantetheine cofactors in fibroblast derived from PKAN patients. These proteins include cytosolic acyl carrier protein (ACP), which is integrated within the multifunctional polypeptide chain of the fatty acid synthase involved in cytosolic fatty acid biosynthesis type I (FASI); mitochondrial ACP (mtACP) associated with mitocondrial fatty acid biosynthesis type II (FASII); mitochondrial alpha-aminoadipic semialdehyde synthase (AASS); and 10-formyltetrahydrofolate dehydrogenases (cytosolic, ALD1L1, and mitochondrial, ALD1L2). Results: In PKAN fibroblasts the expression levels of cytosolic FAS and ALD1L1 were not affected while the expression levels of mtACP, AASS and ALD1L2 were markedly reduced, suggesting that 4'-phosphopantetheinylation of mitochondrial but no cytosolic proteins were markedly affected in PKAN patients. Furthermore, the correction of PANK2 expression levels by treatment wit
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- 2021
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