This article is part of a series on What kills neurons in neurodegenerative disease?, edited by Todd Golde and Leonard Petrucelli.

Review

Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle

Kristen A Malkus¹ , Elpida Tsika^1,2 and Harry Ischiropoulos^1,3,4

¹  The Joseph Stokes Jr Research Institute, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

²  The Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece

³  Department of Pediatrics, The University of Pennsylvania, Philadelphia, Pennsylvania, USA

⁴  Department of Pharmacology, The University of Pennsylvania, Philadelphia, Pennsylvania, USA

author email corresponding author email

Molecular Neurodegeneration 2009, 4:24doi:10.1186/1750-1326-4-24

Published:	5 June 2009

Abstract

While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD) as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. These intertwined events are the consequence of environmental exposure, genetic factors, and endogenous risks and constitute a "Bermuda triangle" that may be considered the underlying cause of neurodegenerative pathogenesis.