Type-2 alkenes mediate synaptotoxicity in neurodegenerative diseases.

摘要: Synaptic dysfunction appears to be an early pathogenic event in Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease. Although the molecular mechanism of this synaptotoxicity is not known, evidence suggests that these diseases are characterized by a common pathophysiological cascade involving oxidative stress, lipid peroxidation subsequent liberation α,β-unsaturated carbonyl derivatives such as acrolein 4-hydroxy-2-nonenal (HNE). A diverse body vivo vitro data have shown soft electrophilic chemicals can cause nerve terminal damage forming Michael-type adducts with nucleophilic sulfhydryl groups on presynaptic proteins. Therefore, endogenous generation HNE oxidatively stressed neurons certain brain regions might mechanistically related associated neurodegenerative conditions. In addition, members large class structurally known type-2 alkenes. Chemicals (e.g., acrylamide, methylvinyl ketone, methyl acrylate) pervasive pollutants human environments new research has also toxic terminals. review, we provide regional synaptotoxicity, which develops during stages many diseases, mediated HNE. Based presumed site action, propose onset progression neuropathogenic process accelerated environmental exposure other