• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Alzheimer's Disease, Other Dementia, Aging

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

GM1 regulates apoptosis via βsecretase cleavage of APP

  • P1-286
  • 山口 世堯 / Tokiaki Yamaguchi:1 山内 祥生 / Yamauchi Yoshio:1 松本 康之 / Matsumoto Yasuyuki:1 大海 雄介 / Yuhsuke Ohumi:1 古川 圭子 / Furukawa Keiko:2 古川 鋼一 / Furukawa Koichi:1 
  • 1:名古屋大院・医・分子細胞化学 / Div. of Biochem., Inst. of Med., Univ. of Nagoya, Nagoya, Japan 2:中部大学生命健康学部生命医科学科 / Dept. Biomed. Sci., College of Life and Health Sci., Univ. of Chubu, Nagoya, Japan 

Alzheimer disease (AD) is the most common form of dementia. AD is characterized pathologically by the presence of neurofibrillary tangles and amyloid plaque. Previous reports suggest that gangliosides, a type of glyco-sphingolipids, regulate production of amyloid β, a major protein constituent of amyloid plaque, in vivo and vitro.
We have investigated interaction between gangliosides and amyloid β precursor protein (APP) processing. We found an increase of β C-terminal fragments, β-secretase cleavage-products in cells expressing high levels of either one of ganglioside GD2, GM2, or GM1. We further discovered that expression of mature APP was also increased and mature APP was highly localized in lipid rafts in GM1-expressing cells. This is because β secretase cleavage was enhanced in cells expressing ganglioside GM1.
Furthermore, we found an increase of a specific 40 kDa fragment of soluble APP, extracellular domain of APP, in culture medium of cells expressing high levels of ganglioside GM1. We further discovered that GM1-expressing cells were more sensitive to oxidative stress, considered as a cause of neuronal death in AD, than GM1-lacking cells. Moreover, we found that soluble APP, a precursor protein of this fragment, bound to ganglioside GM1 and GD1a, and induced rapid apoptosis only under oxidative stress in GM1-expressing cells compared with GM1-lacking cells.
Our results suggest that ganglioside GM1 promote cell death by regulating intracellular localization and processing of APP, and also function of soluble APP under oxidative stress.

Copyright © Neuroscience2014. All Right Reserved.