T-Cells and excitotoxicity: HIV-1 and other neurodegenerative disorders.
Until recently the central nervous system (CNS) was considered an immune-privileged site, however, technological and immunological advances have resulted in the CNS being reclassified as an "immune-specialized site." The immune cells, particularly T-cells, continuously patrol the brain and are involved in neuroimmune responses. As such, any changes in the brain microenvironment could affect the physiological functioning of T-cells. Particularly, neurotransmission- associated abnormalities, such as excitotoxicity associated with hypersecretion of glutamate, could severely affect the neuroimmune function of T-cells. Excitotoxicity is involved in the pathogenesis of a number of neurodegenerative disorders. The specific excitotoxicity triggered by the excitatory amino acid neurotransmitter, glutamate, is considered a key mechanism involved in neuronal death. The inability of brain immune cells to overcome these aberrant changes is an active area of investigation. In the systemic circulation, glutamate is inversely related to the number of CD4+ T-cells; however, the effects of elevated glutamate and glutamate-induced exicitotoxicity on cells homing in the brain are critical for understanding neuropathogenesis of neurodegenerative disorders.
Mukhtar
Muhammad
M
The Jefferson Institute for Research in Human Virology and Biodefense Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. muhammad.mukhtar@jefferson.edu
Acheampong
Edward
E
Parveen
Zahida
Z
Pomerantz
Roger J
RJ
D015526:AIDS Dementia Complex / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018846:Excitatory Amino Acids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance; D009103:Multiple Sclerosis / Q000276:immunology; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000821:virology
D018846:Excitatory Amino Acids; D018698:Glutamic Acid