Mitochondrial dysfunction associated with increased oxidative stress and α-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue
| العنوان: | Mitochondrial dysfunction associated with increased oxidative stress and α-synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue |
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| المؤلفون: | Masayuki Amagai, Shigeto Sato, Hideki Hayakawa, Makoto Suematsu, Masanobu Shouji, Atsushi Nakanishi, Yasuo Uchiyama, Tomoko Nihira, Takuya Yagi, Wado Akamatsu, Manabu Funayama, Yohei Okada, Yoshikuni Mizuno, Hideki Mochizuki, Noboru Mizushima, Tetsuro Kobayashi, Arifumi Kosakai, Manabu Ohyama, Daisuke Ito, Nobutaka Hattori, Masato Koike, Tomoyoshi Soga, Hideyuki Okano, Masashi Takanashi, Naoko Kuzumaki, Yoichi Imaizumi, Akiyoshi Hirayama, Takako Hishiki, Kozo Hayashi, Norihiro Suzuki |
| المصدر: | Molecular Brain Molecular Brain, Vol 5, Iss 1, p 35 (2012) |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Adult, Male, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Pathology, medicine.medical_specialty, Parkinson's disease, NF-E2-Related Factor 2, Induced Pluripotent Stem Cells, Substantia nigra, Mitochondrion, Biology, medicine.disease_cause, lcsh:RC346-429, Parkin, Mice, Cellular and Molecular Neuroscience, chemistry.chemical_compound, α-synuclein, medicine, Animals, Humans, Molecular Biology, lcsh:Neurology. Diseases of the nervous system, Aged, Membrane Potential, Mitochondrial, Neurons, Alpha-synuclein, Research, Dopaminergic, Brain, Parkinson Disease, Mitochondrial Turnover, Middle Aged, medicine.disease, Pathophysiology, Mitochondria, Cell biology, Oxidative Stress, chemistry, Postmortem Changes, Parkinson’s disease, alpha-Synuclein, Female, Lewy Bodies, Oxidative stress, Signal Transduction |
| الوصف: | Background Parkinson’s disease (PD) is a neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra (SN). The familial form of PD, PARK2, is caused by mutations in the parkin gene. parkin-knockout mouse models show some abnormalities, but they do not fully recapitulate the pathophysiology of human PARK2. Results Here, we generated induced pluripotent stem cells (iPSCs) from two PARK2 patients. PARK2 iPSC-derived neurons showed increased oxidative stress and enhanced activity of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. iPSC-derived neurons, but not fibroblasts or iPSCs, exhibited abnormal mitochondrial morphology and impaired mitochondrial homeostasis. Although PARK2 patients rarely exhibit Lewy body (LB) formation with an accumulation of α-synuclein, α-synuclein accumulation was observed in the postmortem brain of one of the donor patients. This accumulation was also seen in the iPSC-derived neurons in the same patient. Conclusions Thus, pathogenic changes in the brain of a PARK2 patient were recapitulated using iPSC technology. These novel findings reveal mechanistic insights into the onset of PARK2 and identify novel targets for drug screening and potential modified therapies for PD. |
| تدمد: | 1756-6606 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2c81a12ab0db750c22587f0e327017eTest https://doi.org/10.1186/1756-6606-5-35Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d2c81a12ab0db750c22587f0e327017e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17566606 |
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