• Open Access

Living on the edge with too many mouths to feed: Why dopamine neurons die§

Authors

  • J. Paul Bolam PhD,

    Corresponding author
    1. Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, and Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK
    • MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3TH, United Kingdom
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  • Eleftheria K. Pissadaki PhD

    1. Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, and Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK
    2. Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece
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  • Funding agencies: The authors' own work described in this article was supported by the Medical Research Council, UK (grant no.: U138164490), Parkinson's UK (grant nos.: G-0601 and K-1103), and the European Community (FP7: HEALTH-F2-2008-201716).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Although genes, protein aggregates, environmental toxins, and other factors associated with Parkinson's disease (PD) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of PD is the exceptional and selective vulnerability of dopamine (DA) neurons of the SNc. What is it about these neurons, among all other neurons in the brain, that makes them so susceptible in PD? We hypothesize that a major contributory factor is the unique cellular architecture of SNc DA neuron axons. Their large, complex axonal arbour puts them under such a tight energy budget that it makes them particularly susceptible to factors that contribute to cell death, including unique molecular characteristics associated with SNc DA neurons and nonspecific, nervous-system–wide factors. © 2012 Movement Disorder Society

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