Exploitation of the HIV-1 coat glycoprotein, gp120, in neurodegenerative studies in vivo.
Neuronal loss has often been described at post-mortem in the brain neocortex of patients suffering from AIDS. Neuroinvasive strains of HIV infect macrophages, microglial cells and multinucleated giant cells, but not neurones. Processing of the virus by cells of the myelomonocytic lineage yields viral products that, in conjunction with potentially neurotoxic molecules generated by the host, might initiate a complex network of events which lead neurones to death. In particular, the HIV-1 coat glycoprotein, gp120, has been proposed as a likely aetiologic agent of the described neuronal loss because it causes death of neurones in culture. More recently, it has been shown that brain neocortical cell death is caused in rat by intracerebroventricular injection of a recombinant gp120 coat protein, and that this occurs via apoptosis. The latter observation broadens our knowledge in the pathophysiology of the reported neuronal cell loss and opens a new lane of experimental research for the development of novel therapeutic strategies to limit damage to the brain of patients suffering from HIV-associated dementia.
Corasaniti
M T
MT
Faculty of Pharmacy, University of Catanzaro Magna Graecia and IBAF-CNR, Catanzaro, Italy.
Maccarrone
M
M
Nistico
R
R
Malorni
W
W
Rotiroti
D
D
Bagetta
G
G
D000818:Animals; D017209:Apoptosis; D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology*; D015497:HIV-1; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis; D008565:Membrane Proteins; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D009474:Neurons; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D014162:Transfection
D015699:HIV Envelope Protein gp120; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases