Search

Your search keyword '"Friedlander, Robert A."' showing total 946 results
Start Over Author "Friedlander, Robert A."
946 results on '"Friedlander, Robert A."'

2. Biosynthesis of neuroprotective melatonin is dysregulated in Huntingtons disease.

Author

Kim, Jinho, Li, Wei, Wang, Jingjing, Baranov, Sergei, Heath, Brianna, Jia, Jiaoying, Suofu, Yalikun, Baranova, Oxana, Wang, Xiaomin, Larkin, Timothy, Lariviere, William, Carlisle, Diane, and Friedlander, Robert

Subjects
Huntingtons disease, melatonin, mitochondria, Humans, Mice, Animals, Melatonin, Huntington Disease, Pineal Gland
Abstract

Huntingtons disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, AANAT mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.

Published
2023

8. An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma

Author

Casillo, Stephanie M., Gatesman, Taylor A., Chilukuri, Akanksha, Varadharajan, Srinidhi, Johnson, Brenden J., David Premkumar, Daniel R., Jane, Esther P., Plute, Tritan J., Koncar, Robert F., Stanton, Ann-Catherine J., Biagi-Junior, Carlos A.O., Barber, Callie S., Halbert, Matthew E., Golbourn, Brian J., Halligan, Katharine, Cruz, Andrea F., Mansi, Neveen M., Cheney, Allison, Mullett, Steven J., Land, Clinton Van’t, Perez, Jennifer L., Myers, Max I., Agrawal, Nishant, Michel, Joshua J., Chang, Yue-Fang, Vaske, Olena M., MichaelRaj, Antony, Lieberman, Frank S., Felker, James, Shiva, Sruti, Bertrand, Kelsey C., Amankulor, Nduka, Hadjipanayis, Costas G., Abdullah, Kalil G., Zinn, Pascal O., Friedlander, Robert M., Abel, Taylor J., Nazarian, Javad, Venneti, Sriram, Filbin, Mariella G., Gelhaus, Stacy L., Mack, Stephen C., Pollack, Ian F., and Agnihotri, Sameer

Published
2024
Full Text
View/download PDF

9. Impact of Coronavirus Disease 2019 Shutdown on Neurotrauma Volume in Pennsylvania

Author

Algattas, Hanna N, McCarthy, David, Kujawski, Brandon, Agarwal, Nitin, Brown, Joshua, Forsythe, Raquel M, Leonardo, Jody, Walsh, Kevin, Gross, Bradley A, Friedlander, Robert M, Okonkwo, David O, Whiting, Donald, and Miele, Vincent J

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Physical Injury - Accidents and Adverse Effects, Injuries and accidents, Good Health and Well Being, Accidental Falls, Accidents, Traffic, Adolescent, Adult, Aged, Brain Injuries, Traumatic, COVID-19, Female, Humans, Male, Middle Aged, Nervous System Diseases, Pennsylvania, Quarantine, Registries, Trauma Centers, Wounds and Injuries, Wounds, Gunshot, Young Adult, Neurotrauma, Clinical sciences
Abstract

ObjectiveThe 2020 coronavirus disease 2019 (COVID-19) pandemic resulted in state-specific quarantine protocols and introduced the concept of social distancing into modern parlance. We assess the impact of the COVID-19 pandemic on neurotrauma presentations in the first 3 months after shutdown throughout Pennsylvania.MethodsThe Pennsylvania Trauma Systems Foundation was queried for registry data from the Pennsylvania Trauma Outcomes Study between March 12 and June 5 in each year from 2017 to 2020.ResultsAfter the COVID-19 shutdown, there was a 27% reduction in neurotrauma volume, from 2680 cases in 2017 to 2018 cases in 2020, and a 28.8% reduction in traumatic brain injury volume. There was no significant difference in neurotrauma phenotype incurred relative to total cases. Injury mechanism was less likely to be motor vehicle collision and more likely caused by falls, gunshot wound, and recreational vehicle accidents (P < 0.05). Location of injury was less likely on roads and public locations and more likely at indoor private locations (P < 0.05). The proportion of patients with neurotrauma with blood alcohol concentration >0.08 g/dL was reduced in 2020 (11.4% vs. 9.0%; P < 0.05). Mortality was higher during 2020 compared with pre-COVID years (7.7% vs. 6.4%; P < 0.05).ConclusionsDuring statewide shutdown, neurotrauma volume and alcohol-related trauma decreased and low-impact traumas and gunshot wounds increased, with a shift toward injuries occurring in private, indoor locations. These changes increased mortality. However, there was not a change in the types of injuries sustained.

Published
2021

11. A neurodevelopmental epigenetic programme mediated by SMARCD3–DAB1–Reelin signalling is hijacked to promote medulloblastoma metastasis

Author

Zou, Han, Poore, Bradley, Brown, Emily E., Qian, Jieqi, Xie, Bin, Asimakidou, Evridiki, Razskazovskiy, Vladislav, Ayrapetian, Deanna, Sharma, Vaibhav, Xia, Shunjin, Liu, Fei, Chen, Apeng, Guan, Yongchang, Li, Zhengwei, Wanggou, Siyi, Saulnier, Olivier, Ly, Michelle, Fellows-Mayle, Wendy, Xi, Guifa, Tomita, Tadanori, Resnick, Adam C., Mack, Stephen C., Raabe, Eric H., Eberhart, Charles G., Sun, Dandan, Stronach, Beth E., Agnihotri, Sameer, Kohanbash, Gary, Lu, Songjian, Herrup, Karl, Rich, Jeremy N., Gittes, George K., Broniscer, Alberto, Hu, Zhongliang, Li, Xuejun, Pollack, Ian F., Friedlander, Robert M., Hainer, Sarah J., Taylor, Michael D., and Hu, Baoli

Published
2023
Full Text
View/download PDF

15. Cavernous malformations of the central nervous system: An international consensus statement

Author

Tasiou, Anastasia, Brotis, Alexandros G., Kalogeras, Adamantios, Tzerefos, Christos, Alleyne, Cargill H., Jr., Andreou, Alexandros, Demetriades, Andreas K., Foroglou, Nikolaos, Friedlander, Robert M., Karlsson, Bengt, Kitchen, Neil, Meling, Torstein R., Mitsos, Aristotelis, Panagiotopoulos, Vasilios, Papasilekas, Themistoklis, Pavesi, Giacomo, Rasulic, Lukas, Santos, Alejandro N., Spetzler, Robert F., Sure, Ulrich, Tjoumakaris, Stavropoula, Tolias, Christos M., Vajkoczy, Peter, and Fountas, Kostas N.

Published
2023
Full Text
View/download PDF

17. Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome

Author

Golbourn, Brian J., Halbert, Matthew E., Halligan, Katharine, Varadharajan, Srinidhi, Krug, Brian, Mbah, Nneka E., Kabir, Nisha, Stanton, Ann-Catherine J., Locke, Abigail L., Casillo, Stephanie M., Zhao, Yanhua, Sanders, Lauren M., Cheney, Allison, Mullett, Steven J., Chen, Apeng, Wassell, Michelle, Andren, Anthony, Perez, Jennifer, Jane, Esther P., Premkumar, Daniel R. David, Koncar, Robert F., Mirhadi, Shideh, McCarl, Lauren H., Chang, Yue-Fang, Wu, Yijen L., Gatesman, Taylor A., Cruz, Andrea F., Zapotocky, Michal, Hu, Baoli, Kohanbash, Gary, Wang, Xiuxing, Vartanian, Alenoush, Moran, Michael F., Lieberman, Frank, Amankulor, Nduka M., Wendell, Stacy G., Vaske, Olena M., Panigrahy, Ashok, Felker, James, Bertrand, Kelsey C., Kleinman, Claudia L., Rich, Jeremy N., Friedlander, Robert M., Broniscer, Alberto, Lyssiotis, Costas, Jabado, Nada, Pollack, Ian F., Mack, Stephen C., and Agnihotri, Sameer

Published
2022
Full Text
View/download PDF

21. Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release

Author

Suofu, Yalikun, Li, Wei, Jean-Alphonse, Frédéric G, Jia, Jiaoying, Khattar, Nicolas K, Li, Jiatong, Baranov, Sergei V, Leronni, Daniela, Mihalik, Amanda C, He, Yanqing, Cecon, Erika, Wehbi, Vanessa L, Kim, JinHo, Heath, Brianna E, Baranova, Oxana V, Wang, Xiaomin, Gable, Matthew J, Kretz, Eric S, Di Benedetto, Giulietta, Lezon, Timothy R, Ferrando, Lisa M, Larkin, Timothy M, Sullivan, Mara, Yablonska, Svitlana, Wang, Jingjing, Minnigh, M Beth, Guillaumet, Gérald, Suzenet, Franck, Richardson, R Mark, Poloyac, Samuel M, Stolz, Donna B, Jockers, Ralf, Witt-Enderby, Paula A, Carlisle, Diane L, Vilardaga, Jean-Pierre, and Friedlander, Robert M

Subjects
Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Animals, Brain Injuries, Brain Ischemia, Cytochromes c, Male, Melatonin, Mice, Mitochondria, Receptor, Melatonin, MT1, Signal Transduction, mitochondria, G protein-coupled receptor, melatonin, ischemia, neuroprotection
Abstract

G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT1), its associated G protein, and β-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT1 signal-transduction pathway inhibiting stress-mediated cytochrome c release and caspase activation. These findings coupled with our observation that mitochondrial MT1 overexpression reduces ischemic brain injury in mice delineate a mitochondrial GPCR mechanism contributing to the neuroprotective action of melatonin. We propose a new term, "automitocrine," analogous to "autocrine" when a similar phenomenon occurs at the cellular level, to describe this unexpected intracellular organelle ligand-receptor pathway that opens a new research avenue investigating mitochondrial GPCR biology.

Published
2017

25. Targeted Stimulation of the Sensory Afferents Improves Motoneuron Function in Humans With Spinal Muscular Atrophy

Author

Capogrosso, Marco, primary, Prat-Ortega, Genis, additional, Ensel, Scott, additional, Donadio, Serena, additional, Borda, Luigi, additional, Boos, Amy, additional, Yadav, Prakarsh, additional, Verma, Nikhil, additional, Ho, Jonathan, additional, Frazier-Kim, Sarah, additional, Fields, Daryl, additional, Fisher, Lee, additional, Weber, Douglas, additional, Duong, Tina, additional, Weinstein, Steve, additional, Eliasson, Mikael, additional, Montes, Jacqueline, additional, Chen, Karen, additional, Clemens, Paula, additional, Gerzsten, Peter, additional, Mentis, George, additional, Pirondini, Elvira, additional, and Friedlander, Robert, additional

Published
2024
Full Text
View/download PDF

26. Mutant huntingtin disrupts mitochondrial proteostasis by interacting with TIM23

Author

Yablonska, Svitlana, Ganesan, Vinitha, Ferrando, Lisa M., Kim, JinHo, Pyzel, Anna, Baranova, Oxana V., Khattar, Nicolas K., Larkin, Timothy M., Baranov, Sergei V., Chen, Ning, Strohlein, Colleen E., Stevens, Donté A., Wang, Xiaomin, Chang, Yue-Fang, Schurdak, Mark E., Carlisle, Diane L., Minden, Jonathan S., and Friedlander, Robert M.

Published
2019

27. Melatonin inhibits cytosolic mitochondrial DNA-induced neuroinflammatory signaling in accelerated aging and neurodegeneration

Author

Jauhari, Abhishek, Baranov, Sergei V., Suofu, Yalikun, Kim, Jinho, Singh, Tanisha, Yablonska, Svitlana, Li, Fang, Wang, Xiaomin, Oberly, Patrick, Minnigh, M. Beth, Poloyac, Samuel M., Carlisle, Diane L., and Friedlander, Robert M.

Subjects
Brain, Cytokines, Inflammation -- Development and progression, Melatonin, Mitochondrial DNA, Neurons, Health care industry
Abstract

Chronic inflammation is a pathologic feature of neurodegeneration and aging; however, the mechanism regulating this process is not understood. Melatonin, an endogenous free radical scavenger synthesized by neuronal mitochondria, decreases with aging and neurodegeneration. We proposed that insufficient melatonin levels impair mitochondrial homeostasis, resulting in mitochondrial DNA (mtDNA) release and activation of cytosolic DNA- mediated inflammatory response in neurons. We found increased mitochondrial oxidative stress and decreased mitochondrial membrane potential, with higher mtDNA release in brain and primary cerebro-cortical neurons of melatonin- deficient aralkylamine N-acetyltransferase (AANAT) knockout mice. Cytosolic mtDNA activated the cGAS/STING/IRF3 pathway, stimulating inflammatory cytokine generation. We found that Huntington's disease mice had increased mtDNA release, cGAS activation, and inflammation, all inhibited by exogenous melatonin. Thus, we demonstrated that cytosolic mtDNA activated the inflammatory response in aging and neurodegeneration, a process modulated by melatonin. Furthermore, our data suggest that AANAT knockout mice are a model of accelerated aging., Introduction Mitochondrial dysfunction is a common feature of neurodegeneration. Neuronal mitochondrial DNA (mtDNA) damage during neurodegeneration results from reactive oxygen species-initiated (ROS-initiated) oxidation and impairment of DNA repair (1-7). Decreased [...]

Published
2020
Full Text
View/download PDF

33. Mitochondria modulate programmed neuritic retraction

Author

Baranov, Sergei V., Baranova, Oxana V., Yablonska, Svitlana, Suofu, Yalikun, Vazquez, Alberto L., Kozai, Takashi D. Y., Cui, X. Tracy, Ferrando, Lisa M., Larkin, Timothy M., Tyurina, Yulia Y., Kagan, Valerian E., Carlisle, Diane L., Kristal, Bruce S., and Friedlander, Robert M.

Published
2019

34. Congenital and Acquired Chiari Syndrome.

Author

Friedlander, Robert M.

Subjects
*SYRINGOMYELIA, *TONSILLITIS, *SURGICAL decompression, *CEREBROSPINAL fluid shunts, *SYNDROMES, *MEDICAL societies, *ARNOLD-Chiari deformity, *POSTERIOR cranial fossa, *ENCEPHALOCELE
Abstract

The article focuses on Chiari malformation type 1 (CM1), discussing both congenital and acquired forms of the condition. It details the anatomical characteristics where the cerebellar tonsils descend below the foramen magnum, leading to potential obstruction of cerebrospinal fluid (CSF) flow and compression of the brainstem and upper spinal cord. It emphasizes the clinical manifestations such as headaches, neurological symptoms, and the diagnostic criteria involving MRI imaging.

Published
2024
Full Text
View/download PDF

42. Author Correction: Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome

Author

Golbourn, Brian J., Halbert, Matthew E., Halligan, Katharine, Varadharajan, Srinidhi, Krug, Brian, Mbah, Nneka E., Kabir, Nisha, Stanton, Ann-Catherine J., Locke, Abigail L., Casillo, Stephanie M., Zhao, Yanhua, Sanders, Lauren M., Cheney, Allison, Mullett, Steven J., Chen, Apeng, Wassell, Michelle, Andren, Anthony, Perez, Jennifer, Jane, Esther P., Premkumar, Daniel R. David, Koncar, Robert F., Mirhadi, Shideh, McCarl, Lauren H., Chang, Yue-Fang, Wu, Yijen L., Gatesman, Taylor A., Cruz, Andrea F., Zapotocky, Michal, Hu, Baoli, Kohanbash, Gary, Wang, Xiuxing, Vartanian, Alenoush, Moran, Michael F., Lieberman, Frank, Amankulor, Nduka M., Wendell, Stacy G., Vaske, Olena M., Panigrahy, Ashok, Felker, James, Bertrand, Kelsey C., Kleinman, Claudia L., Rich, Jeremy N., Friedlander, Robert M., Broniscer, Alberto, Lyssiotis, Costas, Jabado, Nada, Pollack, Ian F., Mack, Stephen C., and Agnihotri, Sameer

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results