Health & Environmental Research Online (HERO)


Print Feedback Export to File
7427018 
Journal Article 
Pharmacogenomics of Alzheimer's disease: novel therapeutic strategies for drug development 
Cacabelos, R; Cacabelos, P; Torrellas, C; Tellado, I; Carril, JC; , 
2014 
1 
Methods in Molecular Biology
ISSN: 1064-3745
EISSN: 1940-6029 
HUMANA PRESS INC 
TOTOWA 
PHARMACOGENOMICS IN DRUG DISCOVERY AND DEVELOPMENT, 2ND EDITION 
323-556 
English 
25150875 
WOS:000343242600014 
Alzheimer's disease (AD) is a major problem of health and disability, with a relevant economic impact on our society. Despite important advances in pathogenesis, diagnosis, and treatment, its primary causes still remain elusive, accurate biomarkers are not well characterized, and the available pharmacological treatments are not cost-effective. As a complex disorder, AD is a polygenic and multifactorial clinical entity in which hundreds of defective genes distributed across the human genome may contribute to its pathogenesis. Diverse environmental factors, cerebrovascular dysfunction, and epigenetic phenomena, together with structural and functional genomic dysfunctions, lead to amyloid deposition, neurofibrillary tangle formation, and premature neuronal death, the major neuropathological hallmarks of AD. Future perspectives for the global management of AD predict that genomics and proteomics may help in the search for reliable biomarkers. In practical terms, the therapeutic response to conventional drugs (cholinesterase inhibitors, multifactorial strategies) is genotype-specific. Genomic factors potentially involved in AD pharmacogenomics include at least five categories of gene clusters: (1) genes associated with disease pathogenesis; (2) genes associated with the mechanism of action of drugs; (3) genes associated with drug metabolism (phase I and II reactions); (4) genes associated with drug transporters; and (5) pleiotropic genes involved in multifaceted cascades and metabolic reactions. The implementation of pharmacogenomic strategies will contribute to optimize drug development and therapeutics in AD and related disorders. 
Yan, Q; 
978-1-4939-0955-1