Voltage-gated potassium channels in human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorders.
Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD), a severe form of HIV-associated neurocognitive disorders (HAND), describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (brain perivascular macrophages and microglia) releasing immune and viral products in the brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways. Emerging evidence indicates voltage-gated potassium (K(v)) channels, key regulators of cell excitability and animal behavior (learning and memory), are involved in the pathogenesis of HAD/HAND. Here we survey the literature and find that HAD-related alterations in cellular and viral products can increase neuronal K(v) channel activity, leading to neuronal dysfunction and cognitive deficits. Thus, neuronal K(v) channels may be a new target in the effort to develop therapies for HAD and perhaps other inflammatory neurodegenerative disorders.
Keblesh
James
J
Neurophysiology Laboratory, the Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Hu
Dehui
D
Xiong
Huangui
H
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D000818:Animals; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology*; D006801:Humans; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism / Q000502:physiology*
D024642:Potassium Channels, Voltage-Gated