ITIH4 and neurodegenerative disease: Importantly, it is well known that HIV-1 infected macrophages and microglia establish toxic extracellular environments by persistently secreting viral cytotoxic proteins (e.g. gp120 and Tat) and chemicals (e.g. NO), and this toxic environment induces death of nearby neurons in the CNS, leading to HIV-1 associated neurodegenerative diseases [2].