Brain pyrimidine nucleotide synthesis and Alzheimer disease.
Aging (Albany NY)
; 11(19): 8433-8462, 2019 09 27.
Article
em En
| MEDLINE
| ID: mdl-31560653
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosforilação Oxidativa
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Pirimidinas
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Uridina
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Complexo IV da Cadeia de Transporte de Elétrons
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Doença de Alzheimer
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Neurônios
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article