Cell death in HIV dementia.
Many patients infected with human immunodeficiency virus type-1 (HIV-1) suffer cognitive impairment ranging from mild to severe (HIV dementia), which may result from neuronal death in the basal ganglia, cerebral cortex and hippocampus. HIV-1 does not kill neurons by infecting them. Instead, viral proteins released from infected glial cells, macrophages and/or stem cells may directly kill neurons or may increase their vulnerability to other cell death stimuli. By binding to and/or indirectly activating cell surface receptors such as CXCR4 and the N-methyl-D-aspartate receptor, the HIV-1 proteins gp120 and Tat may trigger neuronal apoptosis and excitotoxicity as a result of oxidative stress, perturbed cellular calcium homeostasis and mitochondrial alterations. Membrane lipid metabolism and inflammation may also play important roles in determining whether neurons live or die in HIV-1-infected patients. Drugs and diets that target oxidative stress, excitotoxicity, inflammation and lipid metabolism are in development for the treatment of HIV-1 patients.
Mattson
M P
MP
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. mattsonm@grc.nia.nih.gov
Haughey
N J
NJ
Nath
A
A
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D015696:Gene Products, tat / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D017470:Receptors, Glutamate / Q000378:metabolism; D014764:Viral Proteins / Q000494:pharmacology / Q000633:toxicity; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D044966:Anti-Retroviral Agents; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D018836:Inflammation Mediators; D017470:Receptors, Glutamate; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D002118:Calcium