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Alzheimer's-Focused Administrative Supplement

以阿尔茨海默病为重点的行政补充

基本信息

批准号：
10118339
负责人：
Quasar S Padiath
金额：
$ 24.9万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10118339
关键词：
Administrative Supplement Age of Onset Age-Months Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease patient Animals Applications Grants Architecture Attenuated Behavioral Biochemical Birth Cell Proliferation Cells Chromatin Clinical Data Defect Demyelinating Diseases Demyelinations Development Disease Disease Progression Down-Regulation Doxycycline Drosophila genus Enzyme-Linked Immunosorbent Assay Foundations Functional disorder Future Gene Expression Regulation Gliosis Histologic Impaired cognition Intermediate Filaments Kinetics LMNB1 gene Lamin B1 Lamin Type A Lamin Type B Link Maintenance Measurable Measures Mediating Modeling Mus Mutation Nerve Degeneration Neurofibrillary Tangles Neurons Nuclear Nuclear Inner Membrane Nuclear Lamina Oligodendroglia Pathology Pathway interactions Phenotype Positioning Attribute Premature aging syndrome Progeria Proteins Reporting Role Structure Synapses Syndrome Tauopathies Testing Time Vertebrates Western Blotting Work astrogliosis base behavior test brain tissue clinical phenotype clinically relevant cognitive testing experience experimental study hyperphosphorylated tau leukodystrophy migration mouse model neurodegenerative phenotype neuroinflammation neuron loss normal aging novel overexpression pathological aging role model senescence tau Proteins tau aggregation

项目摘要

Abstract The nuclear lamina is a meshwork of intermediate filaments adjacent to the inner nuclear membrane, integral to all metazoan cells. It performs a critical structural role in the maintenance of nuclear architecture and integration of cytoskeletal structure in addition to aiding in regulation of gene expression, chromatin positioning, cell proliferation, migration and senescence. Exciting, recent work in Drosophila models and from Alzheimer’s diseases (AD) brain tissue has implicated a down regulation, specifically of B type lamins, and nucleoskeletal dysfunction as a critical step mediating the neurodegeneration associated with tauopathies such as AD. Lamin B1 (LB1) is the major B type lamin expressed in the mammalian CNS and loss of this protein during development results in significant defects in neuronal migration and cortical organization. We propose to test the hypothesis that overexpression of LB1 in neurons can provide a neuroprotective effect and ameliorate the phenotype in a mouse model of tau mediated neurodegeneration. The experiments we have proposed will allow us to test the intriguing possibility that modulating the levels of the nuclear lamina protein, LB1 can impact pathology in a clinically relevant mouse model of tau mediated Alzheimer’s disease

摘要

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deletion of conserved non-coding sequences downstream from NKX2-1: A novel disease-causing mechanism for benign hereditary chorea.

DOI：
10.1002/mgg3.1647
发表时间：
2021-04
期刊：
Molecular genetics & genomic medicine
影响因子：
2
作者：
Liao J;Coffman KA;Locker J;Padiath QS;Nmezi B;Filipink RA;Hu J;Sathanoori M;Madan-Khetarpal S;McGuire M;Schreiber A;Moran R;Friedman N;Hoffner L;Rajkovic A;Yatsenko SA;Surti U
通讯作者：
Surti U

Autosomal Dominant Leukodystrophy: A Disease of the Nuclear Lamina.

常染色体显性脑白质营养不良：核层疾病。