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Microtubule Depolymerization Suppresses α-Synuclein Accumulation in a Mouse Model of Multiple System Atrophy

By Kimiko Nakayama, Yasuyo Suzuki and Ikuru Yazawa

Abstract

Multiple system atrophy (MSA) is a neurodegenerative disease caused by an accumulation of α-synuclein (α-syn) in oligodendrocytes. Little is known about the cellular mechanisms by which α-syn accumulation causes neuronal degeneration in MSA. Our previous research, however, revealed that in a mouse model of MSA, oligodendrocytic inclusions of α-syn induced neuronal accumulation of α-syn, as well as progressive neuronal degeneration. Here we identify the mechanisms that underlie neuronal accumulation of α-syn in a mouse MSA model. We found that the α-syn protein binds to β-III tubulin in microtubules to form an insoluble complex. The insoluble α-syn complex progressively accumulates in neurons and leads to neuronal dysfunction. Furthermore, we demonstrated that the neuronal accumulation of insoluble α-syn is suppressed by treatment with a microtubule depolymerizing agent. The underlying pathological process appeared to also be inhibited by this treatment, providing promise for future therapeutic approaches

Topics: Regular Articles
Publisher: American Society for Investigative Pathology
OAI identifier: oai:pubmedcentral.nih.gov:2671377
Provided by: PubMed Central
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