Preventing HIV-1 tat-induced neuronal apoptosis using antioxidant enzymes: Mechanistic and therapeutic implications

HIV-dementia, Tat-induced oxidative stress, and antioxidant therapeutic considerations.

Oxidative stress is thought to play a role in the onset of dementia. HIV-dementia has recently been demonstrated to be associated with oxidative stress as indexed by increased protein and lipid peroxidation in the brain and cerebrospinal fluid compared to HIV non-demented patients. The HIV protein Tat induces neurotoxicity, and, more recently, Tat was found to induce oxidative stress directly a...

Neuronal apoptosis induced by HIV-1 Tat protein and TNF-alpha: potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia.

Apoptosis of neurons and non-neuronal cells has been demonstrated in the brain of AIDS patients with dementia. Previous studies suggest that the apoptotic stimuli are likely to be soluble factors. Several candidates for the soluble factors that lead to neuronal apoptosis in HIV-1 infection have been proposed, including the HIV-1 Tat protein and TNF-alpha. The mechanisms that lead to neuronal ap...

Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120: Mechanistic and Therapeutic Implications

The blood-brain barrier (BBB) is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120) as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP) injection] or chronic [using SV(gp120), an experimental model of ongoing production of gp120] disrupted the BBB, and l...

Therapeutic applications of the cell-penetrating HIV-1 Tat peptide.

Over the past decades, many new therapeutic approaches have been developed for several conditions, including neurodegenerative diseases. However, efficient biodistribution and delivery at biological target sites are hampered by the presence of cell and tissue barriers, and a clinical therapy is prevented by the requirement of invasive administration routes. Candidate drug conjugation to cell-pe...

Apoptosis Through Caspase Activation HIV-1 Tat Induces Microvascular Endothelial