Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1801, Issue 8, Pages 868-877Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2010.01.008
Keywords
Alzheimer disease; Amyloid beta-protein; Ganglioside; Raft
Funding
- Grants-in-Aid for Scientific Research [22300118] Funding Source: KAKEN
Ask authors/readers for more resources
Clarification of the molecular and cellular mechanisms underlying the assembly of amyloid beta-protein (A beta) into insoluble fibrils in the brain has been one of the biggest challenges in the research on Alzheimer disease (AD). We previously identified a novel A beta species, which was characterized by its tight binding to GM1 ganglioside (GM1), in the brain showing early pathological changes of AD. The ganglioside-bound A beta (GA beta) possessed unique characteristics, including its altered immunoreactivity, which suggests its distinct conformation from native A beta, and its strong potency to accelerate A beta assembly into fibrils. On the basis of these characteristics, it was hypothesized that A beta, adopts an altered conformation following interaction with GM1, leading to the generation of GA beta, and then GA beta acts as an endogenous seed for Alzheimer amyloid in the brain. To date, various in vitro and in vivo studies on GA beta have revealed how A beta binds to gangliosides, i.e., what are the favorable physicochemical and neurobiological conditions for generating GA beta, and what is the pathological significance of ganglioside-induced A beta assembly in the development of AD. Interestingly, GA beta is favorably generated in the unique ganglioside-enriched (clustered), raft-like microdomains; moreover, amyloid fibrils formed in the presence of gangliosides are neurotoxic. Furthermore, the conformational change of A beta in the presence of ganglioside has been characterized by an NMR study. In this review, we focus on the recent progress of GA beta studies and highlight the possibility that ganglioside binding is the initial and common step in the development of a part of human misfolding-type amyloidoses, including AD. (C) 2010 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available