2001 Fiscal Year Final Research Report Summary
Immunocytochemical studies of NACP/α-synclein mediated neuronal degeneration
| Project/Area Number |
11670972
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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 |
Psychiatric science
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| Research Institution | Tokyo Metropolitan Organization of Medical Research |
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Principal Investigator |
ARIMA Kunimasa Tokyo Institute of Psychiatry, researcher, 東京都精神医学総合研究所, 研究員 (40124482)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOMURA Yuko Tokyo Institute of Psychiatry, researcher, 東京都精神医学総合研究所, 研究員
UEDA Kenji Tokyo Institute of Psychiatry, researcher, 東京都精神医学総合研究所, 主任研究員 (90261180)
NAKAMURA Minako Tokyo Institute of Psychiatry, researcher (40124482)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Parkinson's disease / multiple system atrophy / synuclein / NACP / Neuronal death / conformation disease / fibrinogenesis / tau |
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| Research Abstract |
NACP/α-synuclein, a soluble presynaptic protein, undergoes conformational changes and forms filamentous aggregates in neuronal and glial cells in brains with Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). We carried out immunohistochemical, immunofluolescence, and immuno-electron microscopic (EM) investigation to clarify NACP-filament formation, and subsequent intracellular alteration in neuronal and glial cells. Subjects : Brain tissues of patients with PD, DLB, and MSA were examined. Apanel of anti-NACP antibodies was employed. Results :
(1) NACP-immunoreactive dystrophic neurites (Lewy neurites) were frequently observed in the brain stem of PD/DLB. They shared immunohistochemical features with Lewy bodies in neuronal processes. On immuno-EM, dystrophic neurites were composed of random aggregation of NACP-filaments at the center of processes.
(2) Cellular co-localization of NACP and microtubule-associated tau protein were sometimes confirm
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ed in PD/DLB brains, and therefore its histological classification into four categories was proposed. On immuno-EM, NACP and tau were found to aggregate into two distinctive subsets of filaments in the same neuronal inclusions in PD/DLB.
(3) NACP-filamentous cytoplasmic inclusions were identified in astrocytes in three of 11 MSA brains. These astrocytes contained 12- 15 nm diameter filaments having a fuzzy outer surface, and appeared to undergo cellular degradation.
(4) NACP-filamentous intra-nuclear inclusions were found in neurons and oligodendrocytes in MSA, but not in astrocytes in MSA or neurons or glia in PD/DLB. Conclusions : (1) We consider that dystrophic neurites may interfere axonal transport, and subsequently cause neuronal dysfunction in PD/DLB brains. (2) Aggregation of NACP may collapse the neuronal microtubular system and trigger aggregation and hyper-phosphorylation of tau in PD/DLB brains. (3) Alteration in astrocytic function in the tissue repair process should be considered in addition to well-accepted oligodendroglial and neuronal pathology in MSA. Less
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