Mar 11, 2020

Enhanced activity of glycolytic enzymes in Drosophila and human cell models of Parkinson's disease based on DJ-1 deficiency

bioRxiv
Cristina Solana-ManriqueNuria Paricio

Abstract

Parkinson's disease (PD) is a neurodenerative debilitating disorder characterized by progressive disturbances in motor, autonomic and psychiatric functions. The pathological hallmark of PD is the loss of dopaminergic neurons in the substantia nigra pars compacta, which causes striatal dopamine deficiency. Although most PD cases are sporadic, approximately 5-10% of all patients suffer from monogenic PD forms caused by highly penetrant rare mutations segregating with the disease in families. One of the genes linked to monogenic PD is <DJ-1>. Mutations in <DJ-1> cause autosomal recessive early-onset forms of fPD; however, it has been shown that an over-oxidized and inactive form of the DJ-1 protein is found in the brains of iPD individuals. Valuable insights into potential PD pathogenic mechanisms involving DJ-1 have been obtained from studies in cell and animal PD models based on <DJ-1> deficiency such as <Drosophila>. Flies mutant for the <DJ-1β> gene, the <Drosophila> ortholog of human <DJ-1>, exhibited disease-related phenotypes such as motor defects, increased reactive oxygen species production and high levels of protein carbonylation. In the present study, we show that loss of <DJ-1β> function significantly increased the act...Continue Reading

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Mentioned in this Paper

Mental Disorders
Pharmacologic Substance
Glycolysis
Regulation of Glycolysis
Brain
PARK7
Dopamine
PARK7 protein, human
Reactive Oxygen Species
Autosomal Recessive Polycystic Kidney Disease

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