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2019-10-15

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cc by (c) Pesini et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171192

Brain pyrimidine nucleotide synthesis and Alzheimer disease

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https://doi.org/10.18632/aging.102328

Resum

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.

Matèries

Malaltia d'Alzheimer, Pirimidines

Matèries (anglès)

Alzheimer's disease, Pyrimidines

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

Citació

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. Brain pyrimidine nucleotide synthesis and Alzheimer disease. _Aging_. 2019. Vol. 11, núm. 19, pàgs. 8433-8462. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/171192]

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