| Autor: |
Colla, Emanuela, Schneider, B, Coune, P, Jensen, Ph, Troncoso, Jc, Lee, Mk |
| Přispěvatelé: |
AMER SOC CELL BIOLOGY, Colla, Emanuela, Schneider, B, Coune, P, Jensen, Ph, Troncoso, Jc, Lee, Mk |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
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| Popis: |
In Parkinson's disease (PD) and other α-synucleinopathies, prefibrillar α-synuclein (αS) oligomer is implicated in the pathogenesis. However, toxic αS oligomers observed using in vitro systems are not generally seen to be associated with α-synucleinopathy in vivo. Thus, the pathologic significance of αS oligomers to αS neurotoxicity is unknown. Herein, we show that, αS that accumulate within endoplasmic reticulum (ER)/microsome forms toxic oligomers in mouse and human brain with the α-synucleinopathy. In the mouse model of α-synucleinopathy, αS oligomers initially form before the onset of disease and continue to accumulate with the disease progression. Significantly, treatment of αS transgenic mice with Salubrinal, an anti-ER stress compound that delays the onset of disease, reduces ER accumulation of αS oligomers. These results indicate that αS oligomers with toxic conformation accumulate in ER, and αS oligomer-dependent ER stress is pathologically relevant for PD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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