title: OXPHOS, pyrimidine nucleotides, and Alzheimer's disease: a pharmacogenomics approach.
abstract: We present a new hypothesis on the contribution of a dysfunction of the oxidative phosphorylation system, through a decrease in the de novo synthesis of pyrimidine nucleotides, to the pathogenesis of late onset Alzheimer's disease (AD). In the light of this proposition, different treatments for AD patients, such as enhancing the electron flow downstream the coenzyme Q10 of the mitochondrial respiratory chain or increasing mitochondrial biogenesis or directly providing pyrimidines, would be possible. AD is a multifactorial disorder and not all patients would benefit from these treatments. Those healthy individuals harboring mtDNA haplotypes related to a coupled OXPHOS function would probably be the better candidates for these preventive therapies.
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Pesini
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Eldris
authors.initials: E
authors.lastname: Iglesias
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Garrido
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Bayona-Bafaluy
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Universidad de Zaragoza, Zaragoza, Spain Fundación ARAID, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Pesini
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010597:Pharmacogenetics / Q000379:methods; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis
chemical_list: D004272:DNA, Mitochondrial; D018697:Nootropic Agents; D011742:Pyrimidine Nucleotides
keywords: Alzheimer's disease; coenzyme $Q_{10}$; de novo pyrimidine biosynthesis; dihydroorotate dehydrogenase; mitochondrial DNA; oxidative phosphorylation