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Demonstration of br...
Demonstration of brain region-specific neuronal vulnerability in human iPSC-based model of familial Parkinson's disease
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- Brazdis, Razvan Marius (författare)
- Friedrich-Alexander University Erlangen-Nürnberg,University Hospital Erlangen
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- Alecu, Julian E. (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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- Marsch, Daniel (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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- Dahms, Annika (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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- Simmnacher, Katrin (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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- Lörentz, Sandra (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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- Brendler, Anna (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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- Schneider, Yanni (författare)
- University Hospital Erlangen
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- Marxreiter, Franz (författare)
- University Hospital Erlangen
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- Roybon, Laurent (författare)
- Lund University,Lunds universitet,Stamcellslaboratoriet för sjukdomsmodellering i det centrala nervsystemet,Forskargrupper vid Lunds universitet,IPSC Laboratory for CNS Disease Modeling,Lund University Research Groups
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- Winner, Beate (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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- Xiang, Wei (författare)
- University Hospital Erlangen
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- Prots, Iryna (författare)
- Friedrich-Alexander University Erlangen-Nürnberg
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(creator_code:org_t)
- 2020-03-11
- 2020
- Engelska 12 s.
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 29:7, s. 1180-1191
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://academic.oup...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modeled human PD using human-induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence the differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared with PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared with CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared with PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- Av författaren/redakt...
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Brazdis, Razvan ...
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Alecu, Julian E.
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Marsch, Daniel
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Dahms, Annika
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Simmnacher, Katr ...
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Lörentz, Sandra
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visa fler...
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Brendler, Anna
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Schneider, Yanni
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Marxreiter, Fran ...
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Roybon, Laurent
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Winner, Beate
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Xiang, Wei
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Prots, Iryna
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Neurovetenskaper
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
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Human Molecular ...
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Lunds universitet