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Phosphoglycerate kinase is a central leverage point in Parkinson's Disease driven neuronal metabolic deficits. | LitMetric

AI Article Synopsis

  • PGK1 is an enzyme that helps produce energy in cells and is being studied as a way to help treat Parkinson's Disease.
  • Research shows that boosting the activity of PGK1 in brain cells can protect against problems caused by the disease.
  • Scientists found that issues with energy production in nerve cells may be a key reason why some people are more likely to get Parkinson's, making PGK1 an important target for new treatments.

Article Abstract

Phosphoglycerate kinase 1 (PGK1), the first ATP producing glycolytic enzyme, has emerged as a therapeutic target for Parkinson's Disease (PD), since a potential enhancer of its activity was reported to significantly lower PD risk. We carried out a suppressor screen of hypometabolic synaptic deficits and demonstrated that PGK1 is a rate limiting enzyme in nerve terminal ATP production. Increasing PGK1 expression in mid-brain dopamine neurons protected against hydroxy-dopamine driven striatal dopamine nerve terminal dysfunction and modest changes in PGK1 activity dramatically suppressed hypometabolic synapse dysfunction . Furthermore, PGK1 is cross-regulated by PARK7 (DJ-1), a PD associated molecular chaperone, and synaptic deficits driven by PARK20 (Synaptojanin-1) can be reversed by increasing local synaptic PGK1 activity. These data indicate that nerve terminal bioenergetic deficits may underly a spectrum of PD susceptibilities and the identification of PGK1 as the limiting enzyme in axonal glycolysis provides a mechanistic underpinning for therapeutic protection.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592794PMC
http://dx.doi.org/10.1101/2023.10.10.561760DOI Listing

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