期刊
AMERICAN JOURNAL OF INFECTIOUS DISEASES
卷 5, 期 4, 页码 307-313出版社
SCIENCE PUBLICATIONS
DOI: 10.3844/ajidsp.2009.307.313
关键词
Astrocyte; interleukin-1-beta; matrix metalloproteinases; microglia; transforming growth factor-beta
资金
- NINDS [NIH RO1 NS48837-01]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS048837] Funding Source: NIH RePORTER
Problem statement: Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and its cognate targets, the Matrix Metalloproteinases (MMPs), were differentially expressed in human brain samples with or without HIV-1 infection or HIV-1 Encephalitis (HIVE). Approach: A through literature review demonstrated that cell culture models of Central Nervous System (CNS) cell types had been used to illustrate the intricate temporal patterns of TIMP-1/MMP expression, regulated by a variety of inflammatory cytokines. Results: As MMPs and TIMP-1 can significantly altered the extracellular environment and cell signaling, the differential regulation of TIMP-1/MMP expression in neuroinflammation can impact neuronal function and survival in disease conditions. TIMP-1 prosurvival effects had been demonstrated in a variety of cell types including CNS neurons, protecting cells from a wide range of stress and insults. TIMP-1, also known to interact with non-MMP targets, altered cell behavior. In this review, we discussed the possibility that the upregulation of TIMP-1 by glia in acute neuroinflammation may be a neuroprotective response. Conclusion: It will be important to delineate the effects of TIMP-1 on neurons and identify receptors and downstream signaling pathways, in order to evaluate TIMP-1 as a therapeutic strategy for neuroinflammatory and neurodegenerative diseases.
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