Production and Roles of Glial Tissue Inhibitor of Metalloproteinases-1 in Human Immunodeficiency Virus-1-Associated Dementia Neuroinflammation: A Review
C. Chao and A. Ghorpade
DOI : 10.3844/ajidsp.2009.307.313
American Journal of Infectious Diseases
Volume 5, Issue 4
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 pro-survival 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.
© 2009 C. Chao and A. Ghorpade. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.