Indoleamine 2,3-Dioxygenase and AIDS Dementia Complex

Patients infected with human-deficiency virus (HIV)-1 resulting in the development of acquired immusyndrome (AIDS) often develop neurological disease named AIMS Dementia Complex (ADC). The underlyingADC is not clearly understood. Models proposed include a direct toxicity of HIV proteins or productiinteracting with N-methyl D-aspartate (NMDA) receptors. It has been reported that the level of quinoreceptor excitotoxin, was elevated in AIDS patients, which correlated with the severity of neuropsycQuinolinic acid is a product of tryptophan metabolism, and it is induced by interferon-gamma appareninduction of indoleamine 2,3-dioxygenase (INDO), the first enzyme in the extra hepatic metabolism ofTryptophan is also the precursor for the production of serotonin, an important neurotransmitter. Wegamma-inducible INDO enzyme is a key factor responsible for elevated production of quinolinic acid adeficiency found in AIDS patients suffering from ADC. In Phase I of this project, we will transfectcloned in an inducible expression vector and determine whether expression of INDO enzyme would leadproduction of quinolinic acid and diminished production of serotonin. In the event of a direct linkmetabolic changes in quinolinic acid and serotonin, the Phase II project will make transgenic mice eattempts to develop a mouse model of this disease for further studies towards intervention and develapproaches.