Genetic variation of matrix metalloproteinase enzyme in HIV-associated neurocognitive disorder

Abstract

Matrix metalloproteinases (MMPs) play a key role in several diseases such as rheumatoid arthritis, HIV-associated neurological diseases (HAND), multiple sclerosis, osteoporosis, stroke, Alzheimer's disease, certain viral infections of the central nervous system, cancer, and hepatitis C virus. MMPs have been explained with regards to extracellular matrix remodeling, which occurs throughout life and ranges from tissue morphogenesis to wound healing in various processes. MMP are inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs). Matrix metalloproteases act as an interface between host's attack by Tat protein of HIV-1 virus and extracellular matrix, which causes breaches in the endothelial barriers by degrading ECM. This process initiates the dissemination of virus in tissues which can lead to an increase HIV-1 infection. MMPs are diverse and are highly polymorphic in nature, hence associated with many diseases. The main objective of this review is to study the gene expression of MMPs in HIV-related diseases and whether TIMPs and MMPs could be related with disease progression, HIV vulnerability and HAND. In this review, a brief description on the classification, regulation of MMP and TIMP, the effect of different MMPs and TIMPs gene polymorphisms and its expression on HIV-associated diseases have been provided. Previous studies have shown that MMPs polymorphism (MMP-1, MMP-2 MMP3, and MMP9) plays an important role in HIV vulnerability, disease progression and HAND. Further research is required to explore their role in pathogenesis and therapeutic perspective.

Keywords: Genetic polymorphism; HAND; HIV disease progression; MMP; TIMP.