Format

Send to

Choose Destination
Trends Pharmacol Sci. 2017 Jun;38(6):541-555. doi: 10.1016/j.tips.2017.03.010. Epub 2017 Apr 23.

Tipping Points and Endogenous Determinants of Nigrostriatal Degeneration by MPTP.

Author information

1
In vitro Toxicology and Biomedicine, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany. Electronic address: Stefan.Schildknecht@uni-konstanz.de.
2
German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Strasse 27, D-53127 Bonn, Germany.
3
In vitro Toxicology and Biomedicine, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
4
Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA.

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.

KEYWORDS:

MPDP(+); MPP(+); Parkinson’s disease; astrocytes; autoxidation

PMID:
28442167
DOI:
10.1016/j.tips.2017.03.010
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center