Document Detail


Toxin models of mitochondrial dysfunction in Parkinson's disease.
MedLine Citation:
PMID:  21554057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SIGNIFICANCE: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity.
RECENT ADVANCES: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology.
CRITICAL ISSUES: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD.
FUTURE DIRECTIONS: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide disease-modifying therapeutics for human PD patients.
Authors:
Terina N Martinez; J Timothy Greenamyre
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2011-07-12
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  16     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-03-06     Completed Date:  2012-07-09     Revised Date:  2013-11-07    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  920-34     Citation Subset:  IM    
Affiliation:
Pittsburgh Institute for Neurodegenerative Diseases, Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Dopaminergic Neurons / drug effects,  metabolism
Humans
Mitochondria / drug effects,  genetics,  metabolism*
Parkinson Disease, Secondary / chemically induced,  genetics,  metabolism*
Toxins, Biological / adverse effects,  metabolism
Grant Support
ID/Acronym/Agency:
ES018058/ES/NIEHS NIH HHS; NS059806/NS/NINDS NIH HHS; P01 NS059806-02/NS/NINDS NIH HHS; RC1 ES018058-02/ES/NIEHS NIH HHS; T32 NS007391/NS/NINDS NIH HHS; T32 NS007391-11A1/NS/NINDS NIH HHS; T32 NS07391/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Toxins, Biological
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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