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Rev Invest Clin ; 54(5): 437-52, 2002.
Artículo en Español | MEDLINE | ID: mdl-12587419

RESUMEN

The AIDS or HIV associated dementia is a cognitive-motor disease, characterized by a strong deficit of several cognitive processes such as attention, memory, sensory perception, motor control among others. The HIV associated dementia affects 30% of adult to 50% of infant HIV positive subjects. Since neurons are not infected by HIV, its principal target in the brain is microglia. The pathophysiology of this syndrome, therefore, remains to be disclosed. Several hypothesis have been proposed, one of them suggests that opportunistic infections can affect the brain. Another hypothesis suggests that microglia secretes toxic products as a result of HIV infection and those are the ones causing the damage and finally, the hypothesis, suggesting that the brain is damaged as a result of the insult caused by HIV-derived proteins. In vitro studies suggest that the HIVgp120, a viral surface protein, is highly neurotoxic. For example HIVgp120 increases cytoplasmic Ca+2 by two ways: facilitating glutamate neurotransmission increasing Ca+2 conductance, and activating the IP3 pathway, facilitating Ca+2 release from the smooth endoplasmic reticulum. This Ca+2 in turn, activates several internal signaling pathways such as the MAPK pathway. We use an animal model to test the HIVgp120 effect on neurophysiological signals and behavior as well as several pharmacological approaches to prevent the HIVgp120 neurotoxic effects. This review updates with the most recent literature discussing the potential mechanisms implicated in the pathophysiology of the AIDS dementia complex. We, in addition, hope the reader will be able to correlate the clinical symptoms observed in the HIV infected subjects and the HIVgp120-induced behavioral changes observed in animal models. Likewise, we discuss the new drugs we are testing, in order to offer a new pharmacological treatment to the patient.


Asunto(s)
Complejo SIDA Demencia/etiología , Proteína gp120 de Envoltorio del VIH/efectos adversos , VIH-1/fisiología , Microglía/patología , Complejo SIDA Demencia/patología , Complejo SIDA Demencia/fisiopatología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Animales , Fármacos Anti-VIH/farmacología , Señalización del Calcio , Muerte Celular , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Diseño de Fármacos , Potenciales Relacionados con Evento P300 , Ácido Glutámico/fisiología , Proteína gp120 de Envoltorio del VIH/fisiología , Haplorrinos , Humanos , Sistema de Señalización de MAP Quinasas , Enfermedades por Prión/patología , Enfermedades por Prión/veterinaria , Enfermedades por Prión/virología , Receptores de Quimiocina/fisiología , Receptores Virales/fisiología , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Replicación Viral
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