Pharmacogenetics of Neurodegenerative Disorders

  • Ramón CacabelosEmail author
  • Clara Torrellas
  • Pablo Cacabelos
  • María J. Villanueva
  • Sergio Piñeiro
  • Cristina Solveira
Part of the Advances in Predictive, Preventive and Personalised Medicine book series (APPPM, volume 9)


Neurodegenerative disorders (NDDs) (Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington’s disease) represent a major problem of health in developed countries, with an important repercussion in disability and health economics. NDDs pose several challenges to our society and the scientific community: they represent an epidemiological problem and a socio-economic, psychological and family burden; most of them have an obscure/complex pathogenesis; their diagnosis is not easy and lacks specific biomarkers; and their treatment is difficult and inefficient. Most NDDs share some common features: they are polygenic disorders in which genetic, epigenetic and environmental factors are involved; some of them follow a general rule in genomics related to disease onset, clinical course and prognosis; multifactorial dysfunctions in several metabolomic networks lead to functional damage to specific brain circuits; accumulation of toxic proteins (i.e. conformational changes) in the nervous tissue is involved in many cases of NDDs; all of them are costly for society, deteriorating the quality of life of sufferers and increasing disability; and although NDDs do not have a curative treatment, in practice available therapeutics is susceptible to pharmacogenomic intervention.

The genes involved in the pharmacogenomics of drugs to treat NDDs fall into five categories: (i) genes associated with disease pathogenesis (pathogenic genes); (ii) genes associated with the mechanism of action of drugs (mechanistic genes); (iii) genes associated with drug metabolism; (iv) genes associated with drug transporters; and (v) pleiotropic genes involved in multifaceted cascades and metabolic reactions. Pharmacogenomics accounts for 30–90 % variability in pharmacokinetics and pharmacodynamics. Only 20–30 % of the Caucasian population processes normally approximately 60 % of the current drugs which are metabolised via cytochromes CYP2D6, CYP2C9 and CYP2C19. Clinical pharmacogenomics may contribute to personalising pharmacological treatment, predicting patient/drug-dose selection, minimising drug interactions, increasing drug efficacy, and reducing unnecessary costs.


Neurodegenerative disorders Alzheimer’s disease Parkinson’s disease Pharmacogenomics CYP2D6 CYP2C9 CYP2C19 CYP3A4/5 APOE Transporters 


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Ramón Cacabelos
    • 1
    • 2
    Email author
  • Clara Torrellas
    • 1
    • 2
  • Pablo Cacabelos
    • 1
    • 2
  • María J. Villanueva
    • 2
  • Sergio Piñeiro
    • 2
  • Cristina Solveira
    • 2
  1. 1.Genomic MedicineCamilo José Cela UniversityMadridSpain
  2. 2.EuroEspes Biomedical Research CenterInstitute of Medical Science and Genomic MedicineCorunnaSpain

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