Novel p75 neurotrophin receptor ligand stabilizes neuronal calcium, preserves mitochondrial movement and protects against HIV associated neuropathogenesis.

Novel p75 neurotrophin receptor ligand stabilizes neuronal calcium, preserves mitochondrial movement and protects against HIV associated neuropathogenesis. Exp Neurol. 2015 Sep 27; Authors: Meeker RB, Poulton W, Clary G, Schriver M, Longo FM Abstract Human immunodeficiency virus (HIV) rapidly penetrates into the brain and establishes a persistent infection of macrophages/microglia. Activation of these cells by HIV results in the secretion of soluble factors that destabilize neuronal calcium homeostasis, encourage oxidative stress and result in neural damage. This damage is thought to underlie the cognitive-motor dysfunction that develops in many HIV-infected patients. Studies have suggested that neurotrophins may protect neurons from the toxic effects of HIV-associated proteins. To better understand the pathogenic mechanisms and the neuroprotective potential of neurotrophin ligands, we evaluated neuronal damage, calcium homeostasis and mitochondrial functions after exposure of cultured rat neurons directly to HIV gp120 or to conditioned medium from human monocyte-derived macrophages treated with gp120. We then assessed the ability of a new non-peptide p75 neurotrophin receptor ligand, LM11A-31, to stabilize calcium homeostasis and prevent the development of pathology. Each toxic challenge resulted in a delayed accumulation of intracellular calcium coupled to a decrease in the rate of calcium clearance from the cell. The delayed calci...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research