title: The role of chronic self-propagating glial responses in neurodegeneration: implications for long-lived survivors of human immunodeficiency virus.
abstract: Within the last decade there has arisen increasing appreciation of the role of glia-derived immune and neurotrophic cytokines, especially microglia-derived interleukin-1 and astrocyte-derived S100beta, in the pathophysiology of Alzheimer's disease and of neurodegeneration in general. Available evidence now suggests that these neurotrophic and immune cytokines, produced in response to neuronal cell dysfunction or death, may elicit cellular and molecular responses resulting in further activation of glia and glial cytokine secretion, producing a cytokine cycle. In conditions characterized by chronic glial activation this cycle becomes self propagating, promoting further neurodegeneration and subsequent further induction of glial cell activation with production of cytokines. In Alzheimer's disease, for instance, such self-propagation is essential to the progressive accumulation of neuropathological changes that underlie progressive dementia. Conditions that predispose one to Alzheimer-type 'senile' neuropathological changes, and to later development of Alzheimer's disease, also exhibit glial activation and overexpression of glial cytokines, providing further evidence of a pathogenic role for glial activation and cytokine cycle elements in the initiation and propagation of Alzheimer lesions. HIV produces a chronic viral infection of the central nervous system that has been associated with chronic glial activation and overexpression of some of the same cytokines that have been implicated in Alzheimer pathogenesis. These observations, together with established functions of cytokine cycle elements, suggest that chronic HIV infection in sufficiently long-lived HIV-infected individuals might confer additional risk for later development of Alzheimer's disease.
authors.affiliation: Department of Veterans' Affairs Medical Center and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Mrak
authors.forename: W S
authors.initials: WS
authors.lastname: Griffin
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology; D001324:Autoantigens / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D015658:HIV Infections / Q000150:complications / Q000503:physiopathology*; D016489:Head Injuries, Closed / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008954:Models, Biological; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins
chemical_list: D001324:Autoantigens; D002135:Calcium-Binding Proteins; D016207:Cytokines; D007375:Interleukin-1; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins