Tipping Points and Endogenous Determinants of Nigrostriatal Degeneration by MPTP
作者： Stefan Schildknecht , Donato A. Di Monte , Regina Pape , Kim Tieu , Marcel Leist
DOI: 10.1016/J.TIPS.2017.03.010
关键词:
摘要: The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a Parkinson's disease (PD)-like syndrome by inducing degeneration of nigrostriatal dopaminergic neurons. Studies the MPTP model have revealed pathomechanisms underlying neurodegeneration and facilitated development drug treatments for PD. In this review, we provide an update on bioactivation biodistribution, reconcile distinct views energetic failure versus reactive oxygen species (ROS) formation as main drivers MPTP-induced neurodegeneration, describe recently identified intrinsic features system that make it particularly vulnerable to MPTP. We discuss these new perspectives endogenous tipping points tissue homeostasis responsible vicious cycles in relation their relevance novel intervention strategies
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