| Literature DB >> 28442167 |
Stefan Schildknecht1, Donato A Di Monte2, Regina Pape3, Kim Tieu4, Marcel Leist3.
Abstract
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 of the MPTP model have revealed the pathomechanisms underlying dopaminergic neurodegeneration and facilitated the development of drug treatments for PD. In this review, we provide an update on MPTP bioactivation and biodistribution, reconcile the distinct views on energetic failure versus reactive oxygen species (ROS) formation as main drivers of MPTP-induced neurodegeneration, and describe recently identified intrinsic features of the nigrostriatal system that make it particularly vulnerable to MPTP. We discuss these new perspectives on the endogenous tipping points of tissue homeostasis and the drivers responsible for vicious cycles in relation to their relevance for the development of novel intervention strategies for PD.Entities:
Keywords: MPDP(+); MPP(+); Parkinson’s disease; astrocytes; autoxidation
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Year: 2017 PMID： 28442167 DOI： 10.1016/j.tips.2017.03.010
Source DB: PubMed Journal: Trends Pharmacol Sci ISSN： 0165-6147 Impact factor: 14.819