A Conserved Role for Homologs in Protecting Dopaminergic Neurons from Oxidative Stress

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Parkinson's disease is a common movement disorder with no known cure. Its characteristic motor symptoms are primarily caused by the progressive loss of midbrain dopaminergic neurons. Although studies have shown that various environmental and genetic factors both contribute to the development of the disease, the underlying mechanisms remain unknown. Here we use powerful invertebrate model organisms, fruit flies and nematode worms, and identify a new gene required for the survival of dopaminergic neurons. We show that homologs of the p48/ptf1-a gene in both flies and worms are expressed in dopaminergic neurons and mutations in p48 increase the susceptibility of dopaminergic neuron death when animals are under oxidative stress. Importantly, genetic variations in p48 in humans have been detected in the sporadic Parkinson's disease patients, indicating the possibility that similar mechanism might play a role in the death of dopaminergic neurons in humans. Oxidative stress has been regarded as a major pathogenic factor for Parkinson's disease. Our results add evidence to the link between oxidative stress and neurodegeneration, and suggest that p48 mutant flies and worms can be used to study mechanisms of neurodegeneration in Parkinson's disease.

Vyšlo v časopise: A Conserved Role for Homologs in Protecting Dopaminergic Neurons from Oxidative Stress. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004718
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004718

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