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Microtubule depolymerization suppresses alpha-synuclein accumulation in a mouse model of multiple system atrophy.


ABSTRACT: Multiple system atrophy (MSA) is a neurodegenerative disease caused by an accumulation of alpha-synuclein (alpha-syn) in oligodendrocytes. Little is known about the cellular mechanisms by which alpha-syn accumulation causes neuronal degeneration in MSA. Our previous research, however, revealed that in a mouse model of MSA, oligodendrocytic inclusions of alpha-syn induced neuronal accumulation of alpha-syn, as well as progressive neuronal degeneration. Here we identify the mechanisms that underlie neuronal accumulation of alpha-syn in a mouse MSA model. We found that the alpha-syn protein binds to beta-III tubulin in microtubules to form an insoluble complex. The insoluble alpha-syn complex progressively accumulates in neurons and leads to neuronal dysfunction. Furthermore, we demonstrated that the neuronal accumulation of insoluble alpha-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.

SUBMITTER: Nakayama K 

PROVIDER: S-EPMC2671377 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Microtubule depolymerization suppresses alpha-synuclein accumulation in a mouse model of multiple system atrophy.

Nakayama Kimiko K   Suzuki Yasuyo Y   Yazawa Ikuru I  

The American journal of pathology 20090312 4


Multiple system atrophy (MSA) is a neurodegenerative disease caused by an accumulation of alpha-synuclein (alpha-syn) in oligodendrocytes. Little is known about the cellular mechanisms by which alpha-syn accumulation causes neuronal degeneration in MSA. Our previous research, however, revealed that in a mouse model of MSA, oligodendrocytic inclusions of alpha-syn induced neuronal accumulation of alpha-syn, as well as progressive neuronal degeneration. Here we identify the mechanisms that underli  ...[more]

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