Progress in understanding basal ganglia dysfunction as a common target for methamphetamine abuse and HIV-1 neurodegeneration.
HIV-1 infection with concurrent methamphetamine (MA) abuse results in exacerbated neurodegenerative changes and rapid progression of a form of sub-cortical dementia termed HIV-1 associated dementia (HAD). A notable feature of HAD is the involvement of the dopaminergic system manifested as parkinsonian like movement abnormalities. The HIV-1 transactivator of transcription (Tat) protein is very often used in experimental studies trying to understand neurotoxic consequences of HIV-1 infection, since the pathophysiological changes induced by Tat mirrors, in part, the means by which HIV-1 infection of the nervous system results in neuronal damage. Understanding the interaction of Tat and MA in the basal ganglia and the resultant injury to the dopaminergic system in rodent models as well as cell culture will shed light on the dopaminergic pathology occurring in HIV-1 infected-MA abusers. The aim of this review is to update the reader on the current knowledge of MA and HIV-1 neurotoxicity, specifically Tat, and discuss the progress in understanding how MA synergizes with the HIV-1 transactivator protein Tat to damage the basal ganglia.
Theodore
Shaji
S
Department of Neurology, The University of Alabama at Birmingham, USA. stheodore@uab.edu
Cass
Wayne A
WA
Nath
Avindra
A
Maragos
William F
WF
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000503:physiopathology; D019969:Amphetamine-Related Disorders / Q000150:complications; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology* / Q000821:virology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D015696:Gene Products, tat / Q000502:physiology; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000209:etiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D008694:Methamphetamine