Abstract
Parkinson’s disease (PD) is characterized by relatively selective degeneration of dopaminergic neurons in the substantia nigra and loss of dopamine in the striatum. More than 50 epidemiological studies confirmed the low incidence of PD in smokers. Examining the distribution of subtypes of nicotinic acetylcholine receptors (nAChRs) in dopaminergic neurons of nigrostriatal system and its change in PD patients is quite important to elucidate possible neuroprotective cascade triggered by nicotine. Evidences of nAChR-mediated protection against neurotoxicity induced by rotenone, 6- hydroxydopamine (6-OHDA), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are briefly reviewed. In rotenone- and 6-OHDA-induced PD models, nAChR-mediated neuroprotection was blocked not only by α4β2 but also by α7 nAChR antagonists. The survival signal transduction, α7 nAChR-Src family-PI3K-Akt/PKB cascade and subsequent upregulation of Bcl-2, would lead to neuroprotection. These findings suggest that nAChR-mediated neuroprotection is achieved through subtypes of nAChRs and common signal cascades. An early diagnosis and protective therapy with specific nAChR modulations could be effective in delaying the progression of PD.
Keywords: Parkinson's disease, nicotine, nAChR, rotenone, 6-OHDA, MPTP, neurodegenerative, nigrostriatal dopaminergic deficit, smoking in vivo model
Current Drug Targets
Title:α7 Nicotinic Acetylcholine Receptor Mediated Neuroprotection in Parkinson’s Disease
Volume: 13 Issue: 5
Author(s): Jun Kawamata, Syuuichirou Suzuki, Shun Shimohama
Affiliation:
Keywords: Parkinson's disease, nicotine, nAChR, rotenone, 6-OHDA, MPTP, neurodegenerative, nigrostriatal dopaminergic deficit, smoking in vivo model
Abstract: Parkinson’s disease (PD) is characterized by relatively selective degeneration of dopaminergic neurons in the substantia nigra and loss of dopamine in the striatum. More than 50 epidemiological studies confirmed the low incidence of PD in smokers. Examining the distribution of subtypes of nicotinic acetylcholine receptors (nAChRs) in dopaminergic neurons of nigrostriatal system and its change in PD patients is quite important to elucidate possible neuroprotective cascade triggered by nicotine. Evidences of nAChR-mediated protection against neurotoxicity induced by rotenone, 6- hydroxydopamine (6-OHDA), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are briefly reviewed. In rotenone- and 6-OHDA-induced PD models, nAChR-mediated neuroprotection was blocked not only by α4β2 but also by α7 nAChR antagonists. The survival signal transduction, α7 nAChR-Src family-PI3K-Akt/PKB cascade and subsequent upregulation of Bcl-2, would lead to neuroprotection. These findings suggest that nAChR-mediated neuroprotection is achieved through subtypes of nAChRs and common signal cascades. An early diagnosis and protective therapy with specific nAChR modulations could be effective in delaying the progression of PD.
Export Options
About this article
Cite this article as:
Jun Kawamata, Syuuichirou Suzuki, Shun Shimohama , α7 Nicotinic Acetylcholine Receptor Mediated Neuroprotection in Parkinson’s Disease , Current Drug Targets 2012; 13 (5) . https://dx.doi.org/10.2174/138945012800399026
DOI https://dx.doi.org/10.2174/138945012800399026 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Current Prodrug Design for Drug Discovery
Current Pharmaceutical Design The Quest for a Tumor Suppressor Gene Phenotype
Current Molecular Medicine Yeast-Derived β-Glucan in Combination with Anti-Tumor Monoclonal Antibody Therapy in Cancer
Recent Patents on Anti-Cancer Drug Discovery Encountering and Advancing Through Antiangiogenesis Therapy for Gliomas
Current Pharmaceutical Design Biological Evaluation of 8-Hydroxyquinolines as Multi-Target Directed Ligands for Treating Alzheimer’s Disease
Current Alzheimer Research Flavonoids as Sirtuin Modulators
Current Topics in Medicinal Chemistry A Role for Calcineurin in Alzheimers Disease
Current Neuropharmacology Incorporation of Anti-angiogenic Therapies in the Treatment of Epithelial Ovarian Cancer: Current Perspectives and Future Directions
Current Angiogenesis (Discontinued) MicroRNAs Involved in Oxidative Stress Processes Regulating Physiological and Pathological Responses
MicroRNA <i>Larrea tridentata</i> and its Biological Activities
Current Topics in Medicinal Chemistry Implications for CNS Repair of Redox Modulation of Cell Survival, Division and Differentiation
Current Alzheimer Research The Potential of Microalgae for the Production of Bioactive Molecules of Pharmaceutical Interest
Current Pharmaceutical Biotechnology Immunoproteasome in Cancer and Neuropathologies: A New Therapeutic Target?
Current Pharmaceutical Design Prion Protein Peptides as Vaccines
Mini-Reviews in Medicinal Chemistry Heterocyclic Chalcone Analogues as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry The Neurophysiology of Hydrogen Sulfide
Inflammation & Allergy - Drug Targets (Discontinued) The Immune System of Cancer Patients
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Polypharmacology of Approved Anticancer Drugs
Current Drug Targets Perspectives on Medicinal Properties of Mangiferin
Mini-Reviews in Medicinal Chemistry Benzofuran Small Molecules as Potential Inhibitors of Human Protein Kinases. A Review
Current Pharmaceutical Design