Project/Area Number |
11670615
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Hirosaki University (2000) Niigata University (1999) |
Principal Investigator |
WAKABAYASHI Koichi Hirosaki University School of Medicine, Department of Neuropathology, Professor, 医学部, 教授 (50240768)
|
Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hitoshi Brain Research Institute, Niigata University, Department of Pathology, Professor, 脳研究所, 教授 (90206839)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
Keywords | Parkinson's disease / Multiple system atrophy / Alpha-synuclein / Lewy body / Glial cytoplasmic inclusion / Tau / Synphilin-1 / Neuronal cell death / アストロサイト / オリゴデンドログリア |
Research Abstract |
Alpha-Synuclein is a major component of Lewy bodies in Parkinson's disease and dementia with Lewy bodies, as well as of glial cytoplasmic inclusions in multiple system atrophy. Recently, a novel protein called synphilin-1 has been identified that associates with alpha-synuclein, and it has been reported that co-transfection of both alphasynuclein and synphilin-1 in mammalian cells yielded eosinophilic cytoplasmic inclusions resembling Lewy bodies. Immunocytochemical and ultrastructural investigations have now been performed on the brain of patients with various neurodegenerative disorders using anti-synphilin-1 antibodies. These antibodies immunostained the neuropil in a punctate pattern throughout the brain of control subjects. In Parkinson's disease, most Lewy bodies observed in the brainstem were positive for synphilin-1. These Lewy bodies showed intense staining in their central cores, but their peripheral portions were only weakly stained or unstained. Pale bodies and Lewy neurites, which were positive for alpha-synuclein, were synphilin-1-negative. In dementia with Lewy bodies, a small fraction of cortical Lewy bodies were immunolabeled by anti-synphilin-1. In multiple system atrophy, numerous glial cytoplasmic inclusions were positive for synphilin-1. Immunoelectron microscopy revealed that the reaction product was localized within filamentous and circular structures in Lewy bodies. Various neuronal and glial inclusions in neurodegenerative disorders other than Lewy body disease and multiple system atrophy were synphilin-1-negative. These findings suggest that abnormal accumulation of synphilin-1 is specific for brain lesions in which alpha-synuclein is a major component.
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