title: Matrix metalloproteinase dependent cleavage of cell adhesion molecules in the pathogenesis of CNS dysfunction with HIV and methamphetamine.
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.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Research Building EP-16, 3970 Reservoir Rd, Washington, DC 20007, USA. kec84@georgetown.edu
authors.forename: Katherine
authors.initials: K
authors.lastname: Conant
authors.forename: Seung T
authors.initials: ST
authors.lastname: Lim
authors.forename: Brad
authors.initials: B
authors.lastname: Randall
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Maguire-Zeiss
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D019966:Substance-Related Disorders / Q000150:complications / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9