Matrix Metalloproteinase Dependent Cleavage of Cell Adhesion Molecules in the Pathogenesis of CNS Dysfunction with HIV and Methamphetamine

Katherine      Conant; Seung      T. Lim; Brad      Randall; Kathleen      A. Maguire-Zeiss

Abstract

Physiologically appropriate levels of matrix metalloproteinases (MMPs) are likely important to varied aspects of CNS function. In particular, these enzymes may contribute to neuronal activity dependent synaptic plasticity and to cell mobility in processes including stem cell migration and immune surveillance. Levels of MMPs may, however, be substantially increased in the setting of HIV infection with methamphetamine abuse. Elevated MMP levels might in turn influence integrity of the blood brain barrier, as has been demonstrated in published work. Herein we suggest that elevated levels of MMPs can also contribute to microglial activation as well as neuronal and synaptic injury through a mechanism that involves cleavage of specific cell and synaptic adhesion molecules.

Keywords: Matrix metalloproteinase (MMP), synapse, neuron, microglial cell, adhesion, cell adhesion molecule (CAM), methamphetamine, CNS, HAND, SNARE.