000099439 001__ 99439 000099439 005__ 20210302143912.0 000099439 0247_ $$2doi$$a10.18632/aging.102328 000099439 0248_ $$2sideral$$a115270 000099439 037__ $$aART-2019-115270 000099439 041__ $$aeng 000099439 100__ $$0(orcid)0000-0001-9695-7349$$aPesini, Alba 000099439 245__ $$aBrain pyrimidine nucleotide synthesis and Alzheimer disease 000099439 260__ $$c2019 000099439 5060_ $$aAccess copy available to the general public$$fUnrestricted 000099439 5203_ $$aMany patients suffering late-onset Alzheimer disease show a deficit in respiratory complex IV activity. The de novo pyrimidine biosynthesis pathway connects with the mitochondrial respiratory chain upstream from respiratory complex IV. We hypothesized that these patients would have decreased pyrimidine nucleotide levels. Then, different cell processes for which these compounds are essential, such as neuronal membrane generation and maintenance and synapses production, would be compromised. Using a cell model, we show that inhibiting oxidative phosphorylation function reduces neuronal differentiation. Linking these processes to pyrimidine nucleotides, uridine treatment recovers neuronal differentiation. To unmask the importance of these pathways in Alzheimer disease, we firstly confirm the existence of the de novo pyrimidine biosynthesis pathway in adult human brain. Then, we report altered mRNA levels for genes from both de novo pyrimidine biosynthesis and pyrimidine salvage pathways in brain from patients with Alzheimer disease. Thus, uridine supplementation might be used as a therapy for those Alzheimer disease patients with low respiratory complex IV activity. 000099439 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B33-17R$$9info:eu-repo/grantAgreement/ES/ISCIII/PI17-00021$$9info:eu-repo/grantAgreement/ES/ISCIII/PI17-00166 000099439 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000099439 590__ $$a4.831$$b2019 000099439 591__ $$aGERIATRICS & GERONTOLOGY$$b7 / 51 = 0.137$$c2019$$dQ1$$eT1 000099439 591__ $$aCELL BIOLOGY$$b62 / 195 = 0.318$$c2019$$dQ2$$eT1 000099439 592__ $$a1.993$$b2019 000099439 593__ $$aCell Biology$$c2019$$dQ1 000099439 593__ $$aAging$$c2019$$dQ1 000099439 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000099439 700__ $$0(orcid)0000-0003-1508-6516$$aIglesias, Eldris$$uUniversidad de Zaragoza 000099439 700__ $$0(orcid)0000-0002-8585-6371$$aBayona-Bafaluy, M Pilar$$uUniversidad de Zaragoza 000099439 700__ $$0(orcid)0000-0003-0145-3020$$aGarrido-Pérez, Nuria$$uUniversidad de Zaragoza 000099439 700__ $$0(orcid)0000-0002-3587-6622$$aMeade, Patricia$$uUniversidad de Zaragoza 000099439 700__ $$0(orcid)0000-0002-9779-8826$$aGaudó, Paula$$uUniversidad de Zaragoza 000099439 700__ $$0(orcid)0000-0002-1426-3958$$aJiménez-Salvador, Irene$$uUniversidad de Zaragoza 000099439 700__ $$aAndrés-Benito, Pol 000099439 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya, Julio$$uUniversidad de Zaragoza 000099439 700__ $$aFerrer, Isidro 000099439 700__ $$aPesini, Pedro 000099439 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini, Eduardo$$uUniversidad de Zaragoza 000099439 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000099439 773__ $$g11, 19 (2019), 8433-8462$$pAGING-US$$tAGING-US$$x1945-4589 000099439 8564_ $$s3260636$$uhttps://zaguan.unizar.es/record/99439/files/texto_completo.pdf$$yVersión publicada 000099439 8564_ $$s2635494$$uhttps://zaguan.unizar.es/record/99439/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000099439 909CO $$ooai:zaguan.unizar.es:99439$$particulos$$pdriver 000099439 951__ $$a2021-03-02-12:36:32 000099439 980__ $$aARTICLE