AGING BRAIN--IMMUNOHISTOLOGY AND BIOCHEMISTRY
大脑老化——免疫组织学和生物化学
基本信息
- 批准号:2442201
- 负责人:
- 金额:$ 4.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-09-15 至 1997-10-31
- 项目状态:已结题
- 来源:
- 关键词:Alzheimer's disease Downs syndrome adult human (21+) aging antigens complementary DNA electron microscopy fibrous protein gel electrophoresis gene expression histochemistry /cytochemistry human tissue immunochemistry laboratory mouse laboratory rabbit microfilaments microtubules monoclonal antibody neurofibrillary tangles neurofilament proteins nonhistone nucleoprotein nucleic acid sequence paired helical filament protein sequence protein structure
项目摘要
This project is aimed at understanding the biology and molecular
pathogenesis of aging in the nervous system. Alzheimer's disease
(AD), the most common organic dementia seen in old age, is
characterized histopathologically by the presence of
neurofibrillary tangles which consist primarily of paired helical
filaments. AD type of neuropathology is found in subjects with
Down syndrome who lived to middle age. Alzheimer's neurofibrillary
tangles (ANT) and numerous fine processes in the disease affected
brain contain epitopes unique to ANT and epitopes shared with
normal proteins such as neurofilament proteins, microtubule
associated-proteins, and ubiquitin. It is unknown how and when
these different components are incorporated into ANT. Using brain
tissues with Down syndrome from various age groups and
immunocytochemical methods we will determine if there are
differences in the sequence of acquiring various epitopes into the
abnormal structures. In a previous study, we used monoclonal anti-
ANT antibodies to screen a human brain cDNA expression library and
have isolated and characterized a MAP2 cDNA that encodes ANT
epitopes. In continuing studies, we will produce antibodies to
human MAP2 fusion protein in which the known ANT epitopes are
deleted. These antibodies will be used to identify and localize
additional ANT epitopes in MAP2. The position of ANT epitopes in
intact MAP2 molecule will be determined by immunoblotting of the
MAP2 peptide fragments (generated by limited proteolysis and
chemical cleavage) with anti-ANT antibodies. We hope to find out
if ANT-related epitopes are clustered in a specific region of the
MAP2 molecule. Using peptide fragments generated from MAP2 fusion
protein (by lambda gt 11 containing the MAP2 cDNA insert), we will
obtain the partial amino acid sequencing data of small fragments.
This data will allow us to confirm the results obtained from the
sequencing of MAP2 cDNA. Recent studies showed the cross-
reactivity between ubiquitin and neurofibrillary inclusions found
in various neuropathological conditions, suggests that the
ubiquitin system plays a significant role in neurofibrillary
degeneration. In continuing studies, we hope to find out if
neurocytoskeletal proteins are acceptors for ubiqutination, to
compare the distribution of ubiquitin in different neuronal
cytoplasmic compartments, and to determine if cytoskeletal
proteins, under pathological conditions, are ubiquitinated to a
different extent.
该项目旨在了解生物学和分子生物学
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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SHU-HUI C YEN其他文献
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{{ truncateString('SHU-HUI C YEN', 18)}}的其他基金
Biochemistry and Cell Biology of alpha-Synucleinopathies
α-突触核蛋白病的生物化学和细胞生物学
- 批准号:
6842193 - 财政年份:2004
- 资助金额:
$ 4.44万 - 项目类别:
MECHANISMS OF TAU PATHOGENSIS IN A CELL MODEL OF TAUOPATHY
TAU 病变细胞模型中 TAU 发病机制
- 批准号:
6878765 - 财政年份:2004
- 资助金额:
$ 4.44万 - 项目类别:
PATHOBIOLOGY OF NEURODEGENERATIVE DISEASES LINKED TO TAU GENE MUTATIONS
与 TAU 基因突变相关的神经退行性疾病的病理学
- 批准号:
6338597 - 财政年份:2000
- 资助金额:
$ 4.44万 - 项目类别:
PATHOBIOLOGY OF NEURODEGENERATIVE DISEASES LINKED TO TAU GENE MUTATIONS
与 TAU 基因突变相关的神经退行性疾病的病理学
- 批准号:
6205226 - 财政年份:1999
- 资助金额:
$ 4.44万 - 项目类别:
AGING BRAIN--IMMUNOHISTOLOGY AND BIOCHEMISTRY
大脑老化——免疫组织学和生物化学
- 批准号:
3479940 - 财政年份:1993
- 资助金额:
$ 4.44万 - 项目类别:
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