KMID : 1161520060100030115
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Animal Cells and Systems 2006 Volume.10 No. 3 p.115 ~ p.120
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¥á-Synuclein induces unfolded protein response via distinct signaling pathway independent of er-membrane kinases
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Kang Shin-Jung
Shin Ki-Soon Kwon Yun-Hee Kim
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Abstract
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Parkinson¡¯s disease (PD) is a neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Mutations in ¥á?synuclein have been causally linked to the pathogenesis of hereditary PD. In addition, it is a major component of Lewy body found in the brains of sporadic cases as well. In the present study, we examined whether overexpression of wild type or PD?related mutant ¥á?synuclein induces unfolded protein response (UPR) and triggers the known signaling pathway of the resulting endoplasmic reticulum (ER) stress in SH?SY5Y cells. Overexpression of wild type, A30P, and A53T ¥á?synuclein all induced XBP?1 mRNA splicing, one of the late stage UPR events. However, activation of ER membrane kinases and upregulation of ER or cytoplsmic chaperones were not detected when ¥á?synuclein was overexpressed. However, basal level of cytoplsmic calcium was elevated in ¥á?synuclein?expressing cells. Our observation suggests that overexpression of ¥á?synuclein induces UPR independent of the known ER membrane kinase?mediated signaling pathway and induces ER stress by disturbing calcium homeostasis.
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KEYWORD
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¥á-Synuclein, Parkinson¡¯s disease, unfolded protein response, ER stress
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