Brain pyrimidine nucleotide synthesis and Alzheimer disease
| Autor: | Alba Pesini, Paula Gaudó, Eduardo Ruiz-Pesini, Nuria Garrido-Pérez, M. Pilar Bayona-Bafaluy, Isidro Ferrer, Julio Montoya, Pol Andrés-Benito, Irene Jiménez-Salvador, Pedro Pesini, Eldris Iglesias, Patricia Meade |
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| Rok vydání: | 2019 |
| Předmět: |
Aging
Pyrimidine brain oxidative phosphorylation Oxidative phosphorylation Biology Electron Transport Complex IV chemistry.chemical_compound Alzheimer Disease medicine Humans Nucleotide Uridine Neurons chemistry.chemical_classification Cell Differentiation Cell Biology Human brain Pirimidines Alzheimer's disease medicine.disease pyrimidine salvage pathway Mitochondria Cell biology Neuroprotective Agents Mitochondrial respiratory chain medicine.anatomical_structure Malaltia d'Alzheimer Pyrimidines chemistry Drug Design Pyrimidine metabolism pyrimidine biosynthesis de novo Research Paper Signal Transduction |
| Zdroj: | Zaguán: Repositorio Digital de la Universidad de Zaragoza Universidad de Zaragoza Zaguán. Repositorio Digital de la Universidad de Zaragoza instname Dipòsit Digital de la UB Universidad de Barcelona Aging (Albany NY) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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