Parkinson's disease: Mechanisms and models

William Dauer, Serge Przedborski

Research output: Contribution to journalReview article

3148 Citations (Scopus)

Abstract

Parkinson's disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Current PD medications treat symptoms; none halt or retard dopaminergic neuron degeneration. The main obstacle to developing neuroprotective therapies is a limited understanding of the key molecular events that provoke neurodegeneration. The discovery of PD genes has led to the hypothesis that misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are pivotal to PD pathogenesis. Previously implicated culprits in PD neurodegeneration, mitochondrial dysfunction and oxidative stress, may also act in part by causing the accumulation of misfolded proteins, in addition to producing other deleterious events in dopaminergic neurons. Neurotoxin-based models (particularly MPTP) have been important in elucidating the molecular cascade of cell death in dopaminergic neurons. PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.

Original languageEnglish (US)
Pages (from-to)889-909
Number of pages21
JournalNeuron
Volume39
Issue number6
DOIs
StatePublished - Sep 11 2003
Externally publishedYes

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Dopaminergic Neurons
Parkinson Disease
Substantia Nigra
Nerve Degeneration
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Neurotoxins
Proteasome Endopeptidase Complex
Ubiquitin
Genes
Proteins
Oxidative Stress
Cell Death

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Parkinson's disease : Mechanisms and models. / Dauer, William; Przedborski, Serge.

In: Neuron, Vol. 39, No. 6, 11.09.2003, p. 889-909.

Research output: Contribution to journalReview article

Dauer, William ; Przedborski, Serge. / Parkinson's disease : Mechanisms and models. In: Neuron. 2003 ; Vol. 39, No. 6. pp. 889-909.
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