Alpha7 nicotinic receptors as therapeutic targets for Parkinson's disease

Biochem Pharmacol. 2015 Oct 15;97(4):399-407. doi: 10.1016/j.bcp.2015.06.014. Epub 2015 Jun 18.

Abstract

Accumulating evidence suggests that CNS α7 nicotinic acetylcholine receptors (nAChRs) are important targets for the development of therapeutic approaches for Parkinson's disease. This progressive neurodegenerative disorder is characterized by debilitating motor deficits, as well as autonomic problems, cognitive declines, changes in affect and sleep disturbances. Currently l-dopa is the gold standard treatment for Parkinson's disease motor problems, particularly in the early disease stages. However, it does not improve the other symptoms, nor does it reduce the inevitable disease progression. Novel therapeutic strategies for Parkinson's disease are therefore critical. Extensive pre-clinical work using a wide variety of experimental models shows that nicotine and nAChR agonists protect against damage to nigrostriatal and other neuronal cells. This observation suggests that nicotine and/or nAChR agonists may be useful as disease modifying agents. Additionally, studies in several parkinsonian animal models including nonhuman primates show that nicotine reduces l-dopa-induced dyskinesias, a side effect of l-dopa therapy that may be as incapacitating as Parkinson's disease itself. Work with subtype selective nAChR agonists indicate that α7 nAChRs are involved in mediating both the neuroprotective and antidyskinetic effects, thus offering a targeted strategy with optimal beneficial effects and minimal adverse responses. Here, we review studies demonstrating a role for α7 nAChRs in protection against neurodegenerative effects and for the reduction of l-dopa-induced dyskinesias. Altogether, this work suggests that α7 nAChRs may be useful targets for reducing Parkinson's disease progression and for the management of the dyskinesias that arise with l-dopa therapy.

Keywords: Alpha7; Neuroprotection; Nicotinic receptors; Parkinson's disease; l-dopa-induced dyskinesias.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiparkinson Agents / pharmacology*
  • Humans
  • Nicotinic Agonists / pharmacology*
  • Parkinson Disease / drug therapy*
  • alpha7 Nicotinic Acetylcholine Receptor / agonists*
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

  • Antiparkinson Agents
  • Nicotinic Agonists
  • alpha7 Nicotinic Acetylcholine Receptor