期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
卷 50, 期 -, 页码 157-186出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.pharmtox.010909.105753
关键词
lysophosphatidic acid; G protein-coupled receptor; autotaxin; brain; cancer; development
资金
- NIH [MH051699, NS048478, HD050685]
- Agency of Science, Technology, and Research National Science Scholarship, Singapore
- National Science Foundation
- NIH/NICHD
- NIDA Diversity Supplement Grant
- Scripps Translational Science Institute Pilot Study Award
- Novartis
- Korea Research Foundation [KRF-2006-352-E00018, KRF-2004-214-C00246]
- Capita Foundation Research Grant
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD050685] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025774] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH051699, R29MH051699] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS048478] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA019674] Funding Source: NIH RePORTER
Lysophosphatidic acid (LPA) is a small, ubiquitous phospholipid that acts as an extracellular signaling molecule by binding to and activating at least five known G protein-coupled receptors (GPCRs): LPA(1)-LPA(5). They are encoded by distinct genes named LPAR1-LPAR5 in humans and Lpar1-Lpar5 in mice. The biological roles of LPA are diverse and include developmental, physiological, and pathophysiological effects. I This diversity is mediated by broad and overlapping expression patterns and multiple downstream signaling pathways activated by cognate LPA receptors. Studies using cloned receptors and genetic knockout mice have been instrumental in uncovering the significance of this signaling system, notably involving basic cellular processes as well as multiple organ Systems Such,IS the nervous system. This has further provided valuable proof-of-concept data to support LPA receptors and LPA metabolic enzymes as targets for the treatment of medically important diseases that include neuropsychiatric disorders, neuropathic pain, infertility, cardiovascular disease, inflammation, fibrosis, and cancer.
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