Caspase Cascades in Human Immunodeficiency Virus-Associated Neurodegeneration

• DOI: 10.1523/jneurosci.22-10-04015.2002
• Publication Date: 2018-04-04T23:40:38Z
• Authors: Gwenn A. Garden; Samantha L. Budd; Elena Tsai; Lisa Hanson; Marcus Kaul; Danielle M. D'Emilia; Robert M. Friedla...; Junying Yuan; Eliezer Masliah; Stuart A. Lipton
• Keywords: XIAP

Many patients infected with human immunodeficiency virus-1 (HIV-1) develop a syndrome of neurologic deterioration known as HIV-associated dementia (HAD). Neurons are not productively by HIV-1; thus, the mechanism HIV-induced neuronal injury remains incompletely understood. Several investigators have observed evidence injury, including dendritic degeneration, and apoptosis in CNS tissue from HAD. Caspase enzymes, proteases associated process apoptosis, synthesized inactive proenzymes activated proteolytic cascade after exposure to apoptotic signals. Here we demonstrate that HAD is active caspase-3-like immunoreactivity localized soma dendrites neurons affected regions brain. Additionally, caspase activation was studied using an vitro model apoptosis. Increased caspase-3 activity mitochondrial release cytochrome c were cerebrocortical cultures exposed HIV coat protein gp120. Specific inhibitors both Fas/tumor necrosis factor-α/death receptor pathway prevented gp120-induced inhibition also dendrite degeneration vivo transgenic mice expression HIV/gp120. These findings suggest pharmacologic interventions aimed at enzyme pathways may be beneficial for prevention or treatment