Neuroprotective mechanisms of brain-derived neurotrophic factor against 3-nitropropionic acid toxicity: therapeutic implications for Huntington's disease.
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.
Wu
Chia-Lin
CL
Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
Hwang
Chi-Shin
CS
Chen
Shang-Der
SD
Yin
Jiu-Haw
JH
Yang
Ding-I
DI
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000628:therapy; D008928:Mitochondria / Q000378:metabolism; D009574:Nitro Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011422:Propionates / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D053823:Hedgehog Proteins; D009574:Nitro Compounds; D011422:Propionates; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C015392:3-nitropropionic acid