演題詳細
Poster
パーキンソン病とその類縁疾患
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) |
多系統萎縮症におけるオリゴデンドロサイト由来シスタチンCが神経細胞のα-synuclein蓄積を誘導する
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.