Ganglioside-Mediated Assembly of Amyloid β-Protein: Roles in Alzheimer's Disease

Progress in Molecular Biology and Translational Science
Katsumi MatsuzakiKatsuhiko Yanagisawa

Abstract

Assembly and deposition of amyloid β-protein (Aβ) is an early and invariable pathological event of Alzheimer's disease (AD), a chronic neurodegenerative disease affecting the neurons in the brain of aging population. Thus, clarification of the molecular mechanism underlying Aβ assembly is crucial not only for understanding the pathogenesis of AD, but also for developing disease-modifying remedies. In 1995, ganglioside-bound Aβ (GAβ), with unique molecular characteristics, including its altered immunoreactivity and its conspicuous ability to accelerate Aβ assembly, was discovered in an autopsied brain showing early pathological changes of AD. Based on these findings, it was hypothesized that GAβ is an endogenous seed for amyloid fibril formation in the AD brain. A body of evidence that supports the GAβ hypothesis has been growing for over 20years as follows. First, the conformational changes of Aβ from a random coil to an α-helix, and then to a β-sheet in the presence of ganglioside were validated by several techniques. Second, the seed activity of GAβ to accelerate the assembly of soluble Aβ into amyloid fibrils was confirmed by various in vitro and in vivo experiments. Third, it was found that the Aβ binding to ganglioside to ...Continue Reading

Citations

Mar 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Masahiro KawaharaKen-Ichiro Tanaka
Jan 26, 2021·ACS Chemical Neuroscience·Siddhartha BanerjeeYuri L Lyubchenko
Jan 9, 2020·Advanced Drug Delivery Reviews·Simone M CrivelliPilar Martinez-Martinez
Apr 4, 2021·International Journal of Molecular Sciences·Maho Yagi-UtsumiKoichi Kato
Jul 3, 2021·International Journal of Molecular Sciences·Arnaud MarquetteBurkhard Bechinger
Nov 20, 2021·Biophysical Journal·Maria J SarmentoRadek Šachl

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