Neuroprotective mechanisms of brain-derived neurotrophic factor against 3-nitropropionic acid toxicity: therapeutic implications for Huntington's disease

摘要

3-Nitropropionic acid (3-NP) is an irreversible inhibitor of mitochondrial succinate dehydrogenase that has been used to explore the molecular mechanisms of cell death associated with mitochondrial dysfunction and neurodegeneration for Huntington's disease (HD). Brain-derived neurotrophic factor (BDNF) is a neurotrophin that may regulate neuronal survival and differentiation. Experimental evidence derived from both clinical as well as basic research suggests a close association between BDNF deficiency and HD pathogenesis. In this review, we focus on recent progress in the molecular mechanisms responsible for the BDNF-mediated neuroprotective effects against mitochondrial dysfunction induced by 3-NP. Delineation of BDNF-mediated neuroprotective actions against 3-NP toxicity may add in the development of therapeutic intervention for HD where mitochondrial dysfunction is known to play a crucial role in pathogenesis of this devastating disease.