Cacabelos Ramón, Torrellas Clara, Teijido Oscar, Carril Juan Carlos
Department of Genomic Medicine, Camilo José Cela University, Madrid, Spain.
EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Corunna, Spain.
Pharmacogenomics. 2016 Jun;17(9):1041-74. doi: 10.2217/pgs-2016-0031. Epub 2016 Jun 13.
The practical pharmacogenetics of Alzheimer's disease (AD) is circumscribed to acetylcholinesterase inhibitors (AChEIs) and memantine. However, pharmacogenetic procedures should be applied to novel strategies in AD therapeutics including: novel AChEIs and neurotransmitter regulators, anti-Aβ treatments, anti-tau treatments, pleiotropic products, epigenetic drugs and combination therapies. Genes involved in the pharmacogenetic network are under the influence of the epigenetic machinery which regulates gene expression transcriptionally and post-transcriptionally, configuring the fundamentals of pharmacoepigenomics. Over 60% of AD patients present concomitant pathologies demanding additional treatments which increase the likelihood of drug-drug interactions. Lipid metabolism dysfunction is a pathogenic mechanism inherent to AD neurodegeneration. The therapeutic response to hypolipidemic compounds is influenced by the APOE and CYP genotypes. The development of novel compounds and the use of combination/multifactorial treatments require the implantation of pharmacogenomic procedures for the avoidance of ADRs and the optimization of therapeutics.
阿尔茨海默病（AD）的实用药物遗传学局限于乙酰胆碱酯酶抑制剂（AChEIs）和美金刚。然而，药物遗传学程序应应用于AD治疗的新策略，包括：新型AChEIs和神经递质调节剂、抗Aβ治疗、抗tau治疗、多效性产品、表观遗传药物和联合疗法。参与药物遗传学网络的基因受到表观遗传机制的影响，该机制在转录和转录后调节基因表达，构成了药物表观基因组学的基础。超过60%的AD患者存在需要额外治疗的伴随病症，这增加了药物相互作用的可能性。脂质代谢功能障碍是AD神经退行性变固有的致病机制。对降血脂化合物的治疗反应受APOE和CYP基因型的影响。新型化合物的开发以及联合/多因素治疗的使用需要植入药物基因组学程序，以避免不良反应并优化治疗。
