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Parkinson's Disease and Related Disorders

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

Cystatin C causes neuronal inclusions of α-synuclein in multiple system atrophy

  • P1-302
  • 鈴木 康予 / Yasuyo Suzuki:1 金 成花 / Chenghua Jin:1 矢澤 生 / Ikuru Yazawa:1 
  • 1:国立長寿医療研究センター・バイオリソース / Lab Research Resources, Natl center for Geriatrics and Gerontology, Aichi, Japan 

Multiple system atrophy (MSA) is a neurodegenerative disease in which oligodendrocytes and neurons are affected in the central nervous system. MSA is pathologically characterized by abnormal accumulation of α-synuclein inclusions in oligodendrocytes, which are diagnostic of MSA. Accumulation of α-synuclein compromises neuronal function and viability. To clearify how oligodendrocytic α-synuclein inclusions cause neuronal degeneration in MSA, we established primary culture cells derived from transgenic (Tg) mice in which human wild-type α-synuclein was overexpressed selectively in oligodendrocytes. We identified the protein microtubule β-III tubulin, which interacts with α-synuclein to form an insoluble protein complex that progressively accumulates in neurons. The binding of neuronal α-synuclein to β-III tubulin is a key process in the development of neuronal degeneration in the MSA mouse model. We investigated how oligodendrocytic accumulation of α-synuclein causes neuronal accumulation of insoluble α-synuclein. We showed that the expression of α-synuclein was induced by treatment of the conditioned media derived from Tg mouse cell cultures, and neuronal accumulation of α-synuclein was developed in non-Tg mouse cells. Our data suggested that oligodendrocyte-drived signals are induced neuronal α-synuclein accumulation in an MSA model. In the present study, we identify cystatin C that triggers α-synuclein upregulation and insoluble α-synuclein accumulation in neurons. Cystatin C is released by oligodendrocytes derived from Tg mice and extracellular cystatin C increases the expression of the endogenous α-synuclein gene in non-Tg mouse neurons. These neurons then accumulate insoluble α-synuclein, leading to the degeneration. Cystatin C is a pathogenic signal triggering neurodegeneration in MSA.

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