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Review ArticleReview Article

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

Maryka Quik and Susan Wonnacott
Burt M. Sharp, ASSOCIATE EDITOR
Pharmacological Reviews December 2011, 63 (4) 938-966; DOI: https://doi.org/10.1124/pr.110.003269
Maryka Quik
Center for Health Sciences, SRI International, Menlo Park, California (M.Q.); and Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom (S.W.)
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Susan Wonnacott
Center for Health Sciences, SRI International, Menlo Park, California (M.Q.); and Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom (S.W.)
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Burt M. Sharp
Center for Health Sciences, SRI International, Menlo Park, California (M.Q.); and Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom (S.W.)
Roles: ASSOCIATE EDITOR
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Abstract

Parkinson's disease is a debilitating movement disorder characterized by a generalized dysfunction of the nervous system, with a particularly prominent decline in the nigrostriatal dopaminergic pathway. Although there is currently no cure, drugs targeting the dopaminergic system provide major symptomatic relief. As well, agents directed to other neurotransmitter systems are of therapeutic benefit. Such drugs may act by directly improving functional deficits in these other systems, or they may restore aberrant motor activity that arises as a result of a dopaminergic imbalance. Recent research attention has focused on a role for drugs targeting the nicotinic cholinergic systems. The rationale for such work stems from basic research findings that there is an extensive overlap in the organization and function of the nicotinic cholinergic and dopaminergic systems in the basal ganglia. In addition, nicotinic acetylcholine receptor (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for this proposition stems from studies with experimental animal models showing that nicotine protects against neurotoxin-induced nigrostriatal damage and improves motor complications associated with l-DOPA, the “gold standard” for Parkinson's disease treatment. Nicotine interacts with multiple central nervous system receptors to generate therapeutic responses but also produces side effects. It is important therefore to identify the nAChR subtypes most beneficial for treating Parkinson's disease. Here we review nAChRs with particular emphasis on the subtypes that contribute to basal ganglia function. Accumulating evidence suggests that drugs targeting α6β2* and α4β2* nAChR may prove useful in the management of Parkinson's disease.

Footnotes

  • This article is available online at http://pharmrev.aspetjournals.org.

    doi:10.1124/pr.110.003269.

  • © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 63 (4)
Pharmacological Reviews
Vol. 63, Issue 4
1 Dec 2011
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Review ArticleReview Article

α6β2* AND α4β2* NACHRS: DRUG TARGETS FOR PARKINSON'S DISEASE

Maryka Quik and Susan Wonnacott
Pharmacological Reviews December 1, 2011, 63 (4) 938-966; DOI: https://doi.org/10.1124/pr.110.003269

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Review ArticleReview Article

α6β2* AND α4β2* NACHRS: DRUG TARGETS FOR PARKINSON'S DISEASE

Maryka Quik and Susan Wonnacott
Pharmacological Reviews December 1, 2011, 63 (4) 938-966; DOI: https://doi.org/10.1124/pr.110.003269
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  • Article
    • Abstract
    • I. Introduction—Parkinson's Disease and Links to the Nicotinic Cholinergic System
    • II. Inter-Relationship between Nicotinic Cholinergic and Dopaminergic Systems
    • III. Neuronal Nicotinic Acetylcholine Receptors
    • IV. Long-Term Regulation of Nicotinic Acetylcholine Receptors Expression and Function
    • V. Role for Nicotine and Nicotinic Acetylcholine Receptor Ligands in Parkinson's Disease
    • VI. Smoking, Nicotine, and Neuroprotection against Nigrostriatal Damage
    • VII. Nicotine and Symptomatic Improvement
    • VIII. Nicotine and l-DOPA-Induced Dyskinesias
    • IX. Conclusion and Future Directions
    • Acknowledgments
    • Authorship Contributions
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