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Title: Brain pyrimidine nucleotide synthesis and Alzheimer disease
Author: Pesini, Alba
Iglesias, Eldris
Bayona Bafaluy, M. Pilar
Garrido Pérez, Nuria
Meade, Patricia
Gaudó, Paula
Jimenez Salvador, Irene
Andrés Benito, Pol
Montoya, Julio
Ferrer, Isidro (Ferrer Abizanda)
Pesini, Pedro
Ruiz Pesini, Eduardo
Keywords: Malaltia d'Alzheimer
Alzheimer's disease
Issue Date: 15-Oct-2019
Publisher: Impact Journals Llc
Abstract: Many 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.
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It is part of: Aging, 2019, vol. 11, num. 19, p. 8433-8462
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Appears in Collections:Articles publicats en revistes (Institut de Neurociències (UBNeuro))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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