7 results on '"DeJesus-Hernandez, Mariely"'
Search Results
2. Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins
- Author
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Gao, Junli, primary, Mewborne, Quinlan T., additional, Girdhar, Amandeep, additional, Sheth, Udit, additional, Coyne, Alyssa N., additional, Punathil, Ritika, additional, Kang, Bong Gu, additional, Dasovich, Morgan, additional, Veire, Austin, additional, DeJesus Hernandez, Mariely, additional, Liu, Shuaichen, additional, Shi, Zheng, additional, Dafinca, Ruxandra, additional, Fouquerel, Elise, additional, Talbot, Kevin, additional, Kam, Tae-In, additional, Zhang, Yong-Jie, additional, Dickson, Dennis, additional, Petrucelli, Leonard, additional, van Blitterswijk, Marka, additional, Guo, Lin, additional, Dawson, Ted M., additional, Dawson, Valina L., additional, Leung, Anthony K. L., additional, Lloyd, Thomas E., additional, Gendron, Tania F., additional, Rothstein, Jeffrey D., additional, and Zhang, Ke, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Shared brain transcriptomic signature in TDP-43 type A FTLD patients with or without GRN mutations
- Author
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Pottier, Cyril, primary, Mateiu, Ligia, additional, Baker, Matthew C, additional, DeJesus-Hernandez, Mariely, additional, Teixeira Vicente, Cristina, additional, Finch, NiCole A, additional, Tian, Shulan, additional, van Blitterswijk, Marka, additional, Murray, Melissa E, additional, Ren, Yingxue, additional, Petrucelli, Leonard, additional, Oskarsson, Björn, additional, Biernacka, Joanna M, additional, Graff-Radford, Neill R, additional, Boeve, Bradley F, additional, Petersen, Ronald C, additional, Josephs, Keith A, additional, Asmann, Yan W, additional, Dickson, Dennis W, additional, and Rademakers, Rosa, additional
- Published
- 2021
- Full Text
- View/download PDF
4. Shared brain transcriptomic signature in TDP-43 type A FTLD patients with or without GRN mutations.
- Author
-
Pottier, Cyril, Mateiu, Ligia, Baker, Matthew C, DeJesus-Hernandez, Mariely, Vicente, Cristina Teixeira, Finch, NiCole A, Tian, Shulan, Blitterswijk, Marka van, Murray, Melissa E, Ren, Yingxue, Petrucelli, Leonard, Oskarsson, Björn, Biernacka, Joanna M, Graff-Radford, Neill R, Boeve, Bradley F, Petersen, Ronald C, Josephs, Keith A, Asmann, Yan W, Dickson, Dennis W, and Rademakers, Rosa
- Abstract
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a complex heterogeneous neurodegenerative disorder for which mechanisms are poorly understood. To explore transcriptional changes underlying FTLD-TDP, we performed RNA-sequencing on 66 genetically unexplained FTLD-TDP patients, 24 FTLD-TDP patients with GRN mutations and 24 control participants. Using principal component analysis, hierarchical clustering, differential expression and coexpression network analyses, we showed that GRN mutation carriers and FTLD-TDP-A patients without a known mutation shared a common transcriptional signature that is independent of GRN loss-of-function. After combining both groups, differential expression as compared to the control group and coexpression analyses revealed alteration of processes related to immune response, synaptic transmission, RNA metabolism, angiogenesis and vesicle-mediated transport. Deconvolution of the data highlighted strong cellular alterations that were similar in FTLD-TDP-A and GRN mutation carriers with NSF as a potentially important player in both groups. We propose several potentially druggable pathways such as the GABAergic, GDNF and sphingolipid pathways. Our findings underline new disease mechanisms and strongly suggest that affected pathways in GRN mutation carriers extend beyond GRN and contribute to genetically unexplained forms of FTLD-TDP-A. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
5. Poly(ADP-ribose) promotes toxicity of C9ORF72arginine-rich dipeptide repeat proteins
- Author
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Gao, Junli, Mewborne, Quinlan T., Girdhar, Amandeep, Sheth, Udit, Coyne, Alyssa N., Punathil, Ritika, Kang, Bong Gu, Dasovich, Morgan, Veire, Austin, DeJesus Hernandez, Mariely, Liu, Shuaichen, Shi, Zheng, Dafinca, Ruxandra, Fouquerel, Elise, Talbot, Kevin, Kam, Tae-In, Zhang, Yong-Jie, Dickson, Dennis, Petrucelli, Leonard, van Blitterswijk, Marka, Guo, Lin, Dawson, Ted M., Dawson, Valina L., Leung, Anthony K. L., Lloyd, Thomas E., Gendron, Tania F., Rothstein, Jeffrey D., and Zhang, Ke
- Abstract
Arginine-rich dipeptide repeat proteins (R-DPRs), abnormal translational products of a GGGGCC hexanucleotide repeat expansion in C9ORF72, play a critical role in C9ORF72-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the most common genetic form of the disorders (c9ALS/FTD). R-DPRs form liquid condensates in vitro, induce stress granule formation in cultured cells, aggregate, and sometimes coaggregate with TDP-43 in postmortem tissue from patients with c9ALS/FTD. However, how these processes are regulated is unclear. Here, we show that loss of poly(ADP-ribose) (PAR) suppresses neurodegeneration in c9ALS/FTD fly models and neurons differentiated from patient-derived induced pluripotent stem cells. Mechanistically, PAR induces R-DPR condensation and promotes R-DPR–induced stress granule formation and TDP-43 aggregation. Moreover, PAR associates with insoluble R-DPR and TDP-43 in postmortem tissue from patients. These findings identified PAR as a promoter of R-DPR toxicity and thus a potential target for treating c9ALS/FTD.
- Published
- 2022
- Full Text
- View/download PDF
6. Upper motor neuron‐predominant motor neuron disease presenting as atypical parkinsonism: A clinicopathological study.
- Author
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Murakami, Aya, Koga, Shunsuke, Fujioka, Shinsuke, White, Adrianna E., Bieniek, Kevin F., Sekiya, Hiroaki, DeJesus‐Hernandez, Mariely, Finch, NiCole A., van Blitterswijk, Marka, Nakamura, Masataka, Tsuboi, Yoshio, Murray, Melissa E., Wszolek, Zbigniew K., and Dickson, Dennis W.
- Subjects
- *
MOTOR neuron diseases , *AMYOTROPHIC lateral sclerosis , *PROGRESSIVE supranuclear palsy , *FRONTOTEMPORAL lobar degeneration , *PARKINSONIAN disorders , *SYMPTOMS - Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN‐dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN‐predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN‐predominant MND. We reviewed 24 patients with UMN‐predominant MND with TDP‐43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically‐confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically‐confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN‐predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN‐predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN‐predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN‐predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. Shared brain transcriptomic signature in TDP-43 type A FTLD patients with or without GRN mutations.
- Author
-
Pottier C, Mateiu L, Baker MC, DeJesus-Hernandez M, Teixeira Vicente C, Finch NA, Tian S, van Blitterswijk M, Murray ME, Ren Y, Petrucelli L, Oskarsson B, Biernacka JM, Graff-Radford NR, Boeve BF, Petersen RC, Josephs KA, Asmann YW, Dickson DW, and Rademakers R
- Subjects
- Brain metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Humans, Intercellular Signaling Peptides and Proteins genetics, Intercellular Signaling Peptides and Proteins metabolism, Mutation, Transcriptome, Frontotemporal Dementia genetics, Frontotemporal Dementia metabolism, Frontotemporal Lobar Degeneration genetics, Frontotemporal Lobar Degeneration metabolism, Progranulins genetics, Progranulins metabolism
- Abstract
Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a complex heterogeneous neurodegenerative disorder for which mechanisms are poorly understood. To explore transcriptional changes underlying FTLD-TDP, we performed RNA-sequencing on 66 genetically unexplained FTLD-TDP patients, 24 FTLD-TDP patients with GRN mutations and 24 control participants. Using principal component analysis, hierarchical clustering, differential expression and coexpression network analyses, we showed that GRN mutation carriers and FTLD-TDP-A patients without a known mutation shared a common transcriptional signature that is independent of GRN loss-of-function. After combining both groups, differential expression as compared to the control group and coexpression analyses revealed alteration of processes related to immune response, synaptic transmission, RNA metabolism, angiogenesis and vesicle-mediated transport. Deconvolution of the data highlighted strong cellular alterations that were similar in FTLD-TDP-A and GRN mutation carriers with NSF as a potentially important player in both groups. We propose several potentially druggable pathways such as the GABAergic, GDNF and sphingolipid pathways. Our findings underline new disease mechanisms and strongly suggest that affected pathways in GRN mutation carriers extend beyond GRN and contribute to genetically unexplained forms of FTLD-TDP-A., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2022
- Full Text
- View/download PDF
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