遗传多态性（SNPs）在CHRNA7基因对阿尔茨海默病患者对乙酰胆碱酯酶抑制剂（AChEI）的反应的影响

Title:Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer’s Disease

Volume: 18 Issue: 10

关键词: 乙酰胆碱酯酶抑制剂（AChEI），AChEI认知应答，AD发病机制，胆碱能传递，CHRNA7，多奈哌齐，加兰他敏，遗传多态性（SNPs）

摘要: Background: Cholinergic transmission loss is one of the major features in Alzheimer's Disease (AD). Acetylcholinesterase inhibitors (AChEI) are moderately active in AD. α7nAChR (alpha-7 nicotinic acetylcholine receptor), encoded by CHRNA7 (Nicotinic Cholinergic Receptor Alpha-7 gene), is involved in the cholinergic neurotransmission and AD pathogenesis. α7nAChR is a putative receptor of amyloid beta (Aβ). The complex α7nAChR-Aβ is found in neuritic plaques and AD cortical neurons. In normal physiologic conditions, α7nAChR-Aβ interaction leads to receptor activation. Genetic polymorphisms (SNPs) of CHRNA7 and/or CHRFAM7A (fusion gene containing CHRNA7 partial duplication) may be a possible susceptibility trait to dementia, potentially useful to identify high risk or responder individuals. CHRFAM7A-2-bp deletion or CHRNA7 SNPs (rs1514246, rs2337506, rs8027814) seem protective factors in different forms of dementia including AD.

Objective: Correlation between(SNPs) of CHRNA7 and/or CHRFAM7A and cholinesterase inhibitors in AD.

Methods: Literature review.

Results: Among the leading AD therapeutics, Donepezil (DP) and galantamine (AChEI) induce upregulation of α7nAChR protein levels, protecting neurons from degeneration. Patients carrying rs8024987 (C/G) or rs6494223 (C/T) respond better to AChEI. In the caucasic population rs6494223 TT subjects are 7-15% of the total. α7nAChR upregulation induced by DP is higher in lymphocytes from TT subjects than in CC or CT as well as calcium uptake.

Conclusion: The correlation between genetic and functionality data may have an impact on several aspects of disease presentation and therapy, helping in prediction pattern of AD presentation and treatment efficacy. As a consequence it may lead to better patients quality of life and longer periods of self- sufficiency. Moreover, it may contribute to clarify AChEI mechanisms of action.

Cite this article as:

Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer’s Disease, Current Drug Targets 2017; 18 (10) . https://dx.doi.org/10.2174/1389450116666151001111826

DOI https://dx.doi.org/10.2174/1389450116666151001111826	Print ISSN 1389-4501
Publisher Name Bentham Science Publisher	Online ISSN 1873-5592