Role for ER stress responsive ER-Golgi SNARE in processing of Alzheimer`s disease-related protein and autophagy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430072
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyorin University
• Principal Investigator: Suga Kei 杏林大学, 医学部, 講師 (30306675)
• Co-Investigator(Renkei-kenkyūsha): MISHIMA Tatsuya 杏林大学, 医学部, 助教 (40317095) ; KOFUJI Takefumi 杏林大学, 医学部, 助教 (40365200) ; SAITO Ayako 杏林大学, 医学部, 実験助手 (80424109)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 神経科学 / 脳・神経 / ERストレス / アルツハイマー / オートファジー / SNARE / syntaxin / 細胞死

Outline of Final Research Achievements

Ｉam focusing on the role of Syntaxin 5 (Syx5), one of the ER-Golgi SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) protein, in the trafficking and processing of Alzheimer’s disease (AD)-related proteins. In this study, I examined the role of Syntaxin5 (Syx5) in the ER stress-induced autophagy and its effect on the processing of endogenous b-amyloid precursor protein (bAPP) in neuronal cells. I found that the inhibition of bAPP processing caused by ER stress was reversed by the knockdown of Syx5 expression. In addition, there was a positive correlation between the activation of the autophagy flux and the expression level of Syx5 protein. Furthermore, upregulation of Syx5 protein was important for the late stages of autophagy flux. These results suggest that, among ER-Golgi SNAREs, Syx5 is likely to have a role in mediating ER stress-induced autophagy and affecting bAPP processing in neuronal cells.

Free Research Field

神経化学