Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
基本信息
- 批准号:8709755
- 负责人:
- 金额:$ 5.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-01 至 2014-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant):
Lysosomes are acidic, membrane-delimited organelles whose central function is to degrade macromolecules. The lysosome contains a wide variety of soluble enzymes that hydrolyze substrates as well as transmembrane proteins that perform a number of functions including transport of degradation products out of this organelle. The importance of lysosomal proteins in normal cellular physiology is illustrated by the dozens of lysosomal storage disorders (LSDs) such as Tay-Sach's disease where a deficiency in a single lysosomal protein results in accumulation of catabolites and a depletion of downstream metabolites. These monogenic diseases typically cause severe illness including mental retardation, developmental deformities, and premature death. The gene defects in over 40 different LSDs have been identified, which, through genetic counseling, has greatly decreased the prevalence of some of these disorders. Despite this impressive progress, much remains to be accomplished as there are a number of clinically-defined disorders that appear to be LSDs but which are of unknown molecular etiology. In addition, there are numerous individuals that have LSDs based upon clinical and ultrastructural criteria for which the gene defects have not been identified. We hypothesize that many of these unsolved genetic diseases are caused by mutations in genes encoding lysosomal proteins. The overall goal of this proposal is to determine the basis of these unsolved LSD cases. There are two specific aims. Aim 1 is to use a newly developed comparative proteomics method to identify aberrant proteins and the gene defects underlying numerous unsolved LSDs. Aim 2 is to use quantitative mass spectrometry with subcellular fractionation to define the lysosomal proteome and to make this information readily accessible to the biomedical community. This will establish a resource that will greatly facilitate identification of lysosomal disease genes using other approaches such as linkage analysis. Completion of these specific aims will identify new lysosomal disease genes as well as new mutations in existing disease genes that cause atypical clinical presentations. This will be of paramount significant to the affected individuals and families, and will provide important information on how lysosomal deficiencies are manifested. In addition, the proteomics methods established to investigate LSDs will enable future studies on widespread human disorders where lysosomal changes may be important, including cancer and Alzheimer disease. Finally, assignment of the lysosomal proteome will be an important contribution to functional genomics and will have broad biomedical impact.The proposed research is to determine the basis for previously unsolved human genetic diseases. This research will also establish systems for the investigation of the role of a group of biomedically important proteins in widespread human diseases in such as Alzheimer's and cancer.
描述(由申请人提供):
项目成果
期刊论文数量(21)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mass spectrometry-based protein profiling to determine the cause of lysosomal storage diseases of unknown etiology.
基于质谱的蛋白质分析确定病因不明的溶酶体贮积病的原因。
- DOI:10.1074/mcp.m900122-mcp200
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:Sleat,DavidE;Ding,Lin;Wang,Shudan;Zhao,Caifeng;Wang,Yanhong;Xin,Winnie;Zheng,Haiyan;Moore,DirkF;Sims,KatherineB;Lobel,Peter
- 通讯作者:Lobel,Peter
Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins.
人血浆中 6-磷酸甘露糖糖蛋白的鉴定和验证揭示了多种溶酶体和非溶酶体蛋白。
- DOI:10.1074/mcp.m600030-mcp200
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Sleat,DavidE;Wang,Yanhong;Sohar,Istvan;Lackland,Henry;Li,Yan;Li,Hong;Zheng,Haiyan;Lobel,Peter
- 通讯作者:Lobel,Peter
Proteomic analysis of mouse models of Niemann-Pick C disease reveals alterations in the steady-state levels of lysosomal proteins within the brain.
- DOI:10.1002/pmic.201200205
- 发表时间:2012-12
- 期刊:
- 影响因子:3.4
- 作者:Sleat, David E.;Wiseman, Jennifer A.;Sohar, Istvan;El-Banna, Mukarram;Zheng, Haiyan;Moore, Dirk F.;Lobel, Peter
- 通讯作者:Lobel, Peter
Proteomics of the lysosome.
溶酶体的蛋白质组学。
- DOI:10.1016/j.bbamcr.2008.09.018
- 发表时间:2009-04
- 期刊:
- 影响因子:0
- 作者:Lübke T;Lobel P;Sleat DE
- 通讯作者:Sleat DE
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PETER LOBEL其他文献
PETER LOBEL的其他文献
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{{ truncateString('PETER LOBEL', 18)}}的其他基金
Evaluation of the lysosomal protease tripeptidyl peptidase 1 as a potential therapeutic for Alzheimer Disease
溶酶体蛋白酶三肽基肽酶 1 作为阿尔茨海默病潜在治疗剂的评估
- 批准号:
9808153 - 财政年份:2019
- 资助金额:
$ 5.69万 - 项目类别:
A Mass Spectrometry System for Quantitative Proteomics
用于定量蛋白质组学的质谱系统
- 批准号:
8640415 - 财政年份:2014
- 资助金额:
$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
- 批准号:
7992517 - 财政年份:2010
- 资助金额:
$ 5.69万 - 项目类别:
MALDI TOF TOF MASS SPECTROMETER: CELL BIOLOGY
MALDI TOF TOF 质谱仪:细胞生物学
- 批准号:
7166385 - 财政年份:2005
- 资助金额:
$ 5.69万 - 项目类别:
MALDI TOF TOF MASS SPECTROMETER: GENETICS
MALDI TOF TOF 质谱仪:遗传学
- 批准号:
7166384 - 财政年份:2005
- 资助金额:
$ 5.69万 - 项目类别:
TANDEM MASS SPECTROMETER: STRUCTURE OF HIV REVERSE TRANSCRIPTASE WITH SUBSTRATES
串联质谱仪:HIV 逆转录酶与底物的结构
- 批准号:
6973244 - 财政年份:2004
- 资助金额:
$ 5.69万 - 项目类别:
相似海外基金
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
- 批准号:
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新型溶酶体酶
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溶酶体酶与相关人类遗传疾病
- 批准号:
2859210 - 财政年份:1999
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$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
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7466782 - 财政年份:1999
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$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
- 批准号:
7032993 - 财政年份:1999
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$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
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7798945 - 财政年份:1999
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$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
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8241005 - 财政年份:1999
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$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
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6612842 - 财政年份:1999
- 资助金额:
$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
- 批准号:
8050097 - 财政年份:1999
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$ 5.69万 - 项目类别:
Lysosomal Enzymes and Associated Human Genetic Diseases
溶酶体酶和相关人类遗传疾病
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