the role of molecular chaperones in α-synuclein-related diseases
| Project/Area Number |
15590887
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kyoto University |
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Principal Investigator |
KAWAMOTO Yasuhiro Kyoto University, Department of Neurology, Assistant Professor, 医学研究科, 助手 (40335253)
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| Co-Investigator(Kenkyū-buntansha) |
AKIGUCHI Ichiro Ryokoku University, Department of Health Control, Director, 健康管理センター, センター長 (30115779)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | 14-3-3 proteins / α-synuclein / Lewy bodies / glial cytoplsmic inclusions / Lewy body-like hyaline inclusins / immunohistochemistry / astrocytes / molecular chaperones / α-synuclein / パーキンソン病 / 多系統萎縮症 / 筋萎縮性側索硬化症 / クロイツフェルト・ヤコブ病 / 免疫組織化学法 / リン酸化タウ / 脱髄疾患 |
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| Research Abstract |
14-3-3 proteins, a novel type of molecular chaperons, recognizes the phosphoserine-containing motifs of several target proteins, and regulates various types of signal transduction pathways. We have already reported that 14-3-3 immunoreactivity was localized to the α-synuclein-containing inclusins in brains with Parkinso's disease and multiple system atrophy. We then examined the brains and spinal cords of human α-synuclein (A53T) transgenic mice, and found the immunohistochemical colocalization of α-synuclein and 14-3-3 proteins. We also observed the increased immunoreactivities for some heat shock proteins in brains with synucleinopathies. Furthermore, we performed immunohistochemical studies on 14-3-3 proteins using autopsied spinal cord from patients with amyotrophic lateral sclerosis (ALS), and found 14-3-3 immunoreactivity in the Lewy body-like hyaline inclusions from both sporadic and familial ALS cases. We also observed that 14-3-3 immunoreactivity was localized to the α-synuclein-containing inclusinsin in the anterior horn cells from human SOD1(G93T) trausgenic mice. Moreover, we found the enhanced astroglial immunoexpression of 14-3-3 in the demyelinated lesions from patients with multiple sclerosis and progressive multifocal leukoencephalopathy, and in the cortical and subcortical lesions from patients with Creutzfeldt-Jakob disease, and in the ischemic white matter lesions from Binswanger's disease cases. These data suggest that 14-3-3 proteins may play an important role in the formation of several types of inclusions in brains with neurodegenerative diseases, and that 14-3-3 proteins may be induced in astrocytes under various kinds of pathological conditions, including demyelination, inflammation, and ischemia, and may be associated with the formation of astrogliosis.
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Report
(4 results)
Research Products
(18 results)
