期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 174, 期 4, 页码 1471-1480出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2009.080503
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资金
- Ministry of Health, Labor and Welfare, Japan
- Japan Society for the Promotion of Science [20700327]
- Japan Foundation for Aging and Health
- Okinaka Memorial Institute for Medical Research
- Life Science Foundation of Japan
- Grants-in-Aid for Scientific Research [20700327] Funding Source: KAKEN
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. (Am J Pathol 2009, 1174:1471-1480; DOI: 10.2353/ajpath.2009.080503)
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