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What Animal Models of Parkinsonism Tell us About the Distinct Nicotinic Acetylcholine Receptors Involved in Pathogenesis?
Yuri N Utkin*, Elena V Kryukova and Victor I Tsetlin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation
- Corresponding Author:
- Yuri N Utkin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Russian Academy of Sciences
Ul. Miklukho-Maklaya 16/10
Moscow, Russia Federation
Tel: 007 495 336 6522
Fax: +74 95 33 66522
E-mail: utkin@mx.ibch.ru
Received date: February 12, 2015; Accepted date: March 10, 2015; Published date: March 12, 2015
Citation: Utkin YN, Kryukova EV, Tsetlin VI (2015) What Animal Models of Parkinsonism Tell us About the Distinct Nicotinic Acetylcholine Receptors Involved in Pathogenesis? J Alzheimers Dis Parkinsonism 5:181. doi:10.4172/2161-0460.1000181
Copyright: © 2015 Utkin YN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
A prominent degeneration of dopaminergic (DA-ergic) neurons in basal ganglia (striatum and substantia nigra) and a profound loss of dopamine resulting in patient motor dysfunctions are the main characteristics of Parkinson’s disease (PD). The data available indicate a substantial role of nicotinic acetylcholine receptors (nAChR) in molecular mechanisms underlying PD. nAChRs belong to the superfamily of ligand-gated ion channels, their pharmacological profile being determined by an array of subunits forming a distinct receptor subtype. Acetylcholine modulates dopamine release via an interaction with multiple nAChRs subtypes present on the nigrosriatal neurons. This suggests nAChRs as possible targets in the treatment of PD, however the knowledge of subunit composition is necessary for effective drug design. As studies in humans are quite limited, animal models are broadly used for these purposes. For creating experimental Parkinsonism models, low molecular weight toxic organic compounds are commonly used. 1-Methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), 1,1’-Dimethyl-4-4’-bypiridinium dichloride (paraquat), pesticide rotenone and ubiquitin proteasome system inhibitors, such as lactacystin and epoxomicin, can be mentioned as applied more often. Both mammalian and non-mammalian animals are used as model organisms, rodent and non-human primates being used mainly as mammalian models. This review summarizes the data obtained on toxic animal models about the involvement of different nAChR subtypes in PD at different stages. The present data suggest that degeneration of nigrostriatal DA-ergic neurons in the animal PD models is accompanied by alterations in the expression level and functional activity of different nAChR subtypes. Both heterooligomeric α6- and/or α4-containing and α7 homooligomeric subtypes are affected and can be regarded as possible targets for intervention.
