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

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

SHU-HUI C YEN的其他文献

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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:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    6866869
  • 财政年份:
    2004
  • 资助金额:
    $ 4.44万
  • 项目类别:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    7432543
  • 财政年份:
    2004
  • 资助金额:
    $ 4.44万
  • 项目类别:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    7090624
  • 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:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    6948775
  • 财政年份:
    2004
  • 资助金额:
    $ 4.44万
  • 项目类别:
Modeling Neurofibrillary Degeneration
神经原纤维变性建模
  • 批准号:
    7248629
  • 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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