Pharmacogenomics of Alzheimer's and Parkinson's diseases.

Neuroscience Letters
Ramón Cacabelos

Abstract

Neurodegenerative disorders (NDDs)(Alzheimer's disease, Parkinson's disease) represent major problems of health in developed countries, with important psychosocial burden for families and high cost for the society. NDDs share some common pathogenic mechanisms such as age-related decline, multiple genetic defects distributed across the genome, deposits of abnormal proteins in the brain, and diverse environmental risk factors. Patients with NDDs currently receive polypharmacy with a high risk for drug-drug interactions and severe adverse drug events. Pharmacogenomics accounts for 60-90% variability in drug pharmacokinetics and pharmacodynamics. Major determinants of the pharmacogenomic outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic genes. The expression of these genes is under regulatory control of the epigenetic machinery. Approximately, 80% of the Caucasian population is deficient in the metabolization of drugs due to polymorphisms in metabolic genes; consequently, less than 40% of patients respond appropriately to conventional drugs. The implementation of pharmacogenomic procedures in the clinical practice may help to optimize therapeutics in NDDs.

Citations

May 3, 2020·International Journal of Molecular Sciences·Ramon Cacabelos
Sep 19, 2019·Expert Opinion on Drug Discovery·Ramón Cacabelos
Mar 16, 2019·International Journal of Molecular Sciences·Ramón CacabelosDmitry Goldgaber
Nov 18, 2018·International Journal of Molecular Sciences·Ian Simon OlivierVinogran Naidoo
Dec 16, 2020·Emerging Topics in Life Sciences·Parasuraman PadmanabhanBalázs Gulyás
Mar 4, 2021·Expert Opinion on Drug Discovery·Bruno P ImbimboClaudia Balducci
Jun 10, 2021·Medicinal Research Reviews·Ramón CacabelosJuan C Carril
Dec 30, 2021·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Luca DiamantiElisabetta Pupillo

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