Document 0936
 DOCN  M9440936
 TI    HIV-related neurotoxicity.
 DT    9404
 AU    Lipton SA; Department of Neurology, Children's Hospital, Beth Israel;
       Hospital, Brigham.
 SO    Brain Pathol. 1991 Apr;1(3):193-9. Unique Identifier : AIDSLINE
       MED/94122951
 AB    The central nervous system manifestations of AIDS were originally
       thought to consist solely of white matter lesions, but recent evidence
       has shown that a substantial degree of neuronal loss can also occur.
       This review presents evidence for HIV-related toxic factors that may
       account at least in part for this newly-recognized neuronal injury. One
       potential neurotoxin is the HIV-1 envelope glycoprotein gp-120 or a
       fragment of this molecule. This coat protein is shed by the virus and
       potentially released from HIV-infected immune cells. In tissue culture
       experiments on rodent neurons, gp120 produces an early rise in
       intracellular calcium concentration and, subsequently, delayed-onset
       neurotoxicity. In addition, HIV-infected macrophages or microglia
       release as yet undefined toxic factor(s) that kill rodent, chick, and
       human neurons in vitro. It is as yet unknown if one of these macrophage
       toxic factors might represent a gp120 fragment, or alternatively, if
       gp120, in the absence of HIV-1 infection, might be capable of activating
       macrophages to release these toxic factor(s). In at least some neuronal
       cell types, gp120-induced neurotoxicity can be prevented by antagonists
       of L-type voltage-dependent calcium channels or by antagonists of
       N-methyl-D-aspartate (NMDA, a subtype of glutamate receptor).
       Degradation of endogenous glutamate also protects neurons from
       gp120-related neuronal injury, suggesting that gp120 and glutamate are
       both necessary for neuronal cell death as synergistic effectors.
       Antagonists acting at the other types of glutamate receptors (non-NMDA
       antagonists) are ineffective in affording protection from
       gp120.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Animal  Astrocytes/PATHOLOGY  AIDS Dementia Complex/DRUG
       THERAPY/MICROBIOLOGY/PATHOLOGY  Calcium/METABOLISM  Cell Death  Cells,
       Cultured  Human  HIV Envelope Protein gp120/PHYSIOLOGY  HIV
       Infections/*PATHOLOGY  *HIV-1/PHYSIOLOGY  Microglia/PATHOLOGY  Models,
       Biological  Neurons/MICROBIOLOGY/*PATHOLOGY  Neurotoxins/METABOLISM
       Receptors, N-Methyl-D-Aspartate/DRUG EFFECTS/PHYSIOLOGY  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE  REVIEW
       REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).