Macrophages, chemokines and neuronal injury in HIV-1-associated dementia.
Human immunodeficiency virus type-one (HIV- 1)-associated dementia (HAD) is manifested as a spectrum of behavioral, motor and cognitive dysfunctions. The disorder commonly occurs during late stage HIV disease and remains an important complication despite highly active antiretroviral therapies. A metabolic encephalopathy, fueled by neurotoxic secretions from brain mononuclear phagocytes (MP) (macrophages and microglia) underlies HIV- I neuropathogenesis. One pivotal question, however, is how brain MP evolve from neurotrophic to neurotoxic cells. The interplay between the virus, the macrophage and the neuron has just recently begun to be unraveled. Along with a multitude of other MP secretory products, chemokines effect neuronal function by engaging neuronal receptors then activating pathways that alter synaptic transmission, cell growth, injury and protection. Both neurons and glia secrete chemokines. Interestingly, HIV-1 and its gene products can mimic chemokine neuronal signaling by binding to neuronal chemokine receptors or by other non-specific mechanisms. The elucidation of mechanisms involved in chemokine-mediated neural compromise will likely provide unique insights into the pathogenesis and treatment, not only of HAD, but of a wide range of neurodegenerative disorders.
Ryan
Lisa A
LA
Laboratory of Neurotoxicology, Center for Neurovirology and Neurodegenerative Disorders, Omaha, NE 68198-5215, USA.
Cotter
Robin L
RL
Zink
Walter E
WE
Gendelman
Howard E
HE
Zheng
Jialin
J
D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000473:pathology*; D018925:Chemokines / Q000502:physiology*; D015658:HIV Infections / Q000378:metabolism / Q000503:physiopathology; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction
D018925:Chemokines; D019707:Receptors, Chemokine