Neurology and Therapeutics

Biography

Biography: Xin Wang

Abstract

Inappropriate activation of the cell death program drives the progression of amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), as well as increases damage from ischemic stroke. Pharmacological and genetic interventions that inhibit caspases have been shown to slow neurodegeneration in animal models of these chronic illnesses and to lessen the impact of acute brain injury. As in other cells, most physiological pathways leading to cell death include changes in the integrity of mitochondria. Release of mitochondrial cytochrome c into the cytoplasm, often as a consequence of the mitochondrial permeability transition, links upstream events in cell death pathways to activation of capsases that ultimately destroy the cell’s vital structures. Consequently, blocking the release of mitochondrial cytochrome c is the promising strategy to prevent the pathological death of motor neurons, striatal and cortical neurons that cause ALS, HD, and brain injury. We have selected several promising compounds for their ability to prevent cytochrome c release from mitochondria in cultured neurons, drug candidates including melatonin, N-acetyl-L-tryptophan, and N-acetyl-serotonin. Subsequent experiments have shown that these potently neuroprotective agents all exhibit anti-apoptotic activity when used to treat cultured neurons and that they decrease the impact of ALS in mSOD1G93A transgenic ALS mice, or HD in R6/2 transgenic strain whose syndrome resembles HD, or the middle cerebral artery occlusion (MCAO) in C57BL/6 mice that models stroke. The findings may suggest these therapies to be tested in human ALS, HD or stroke patients.