What is it about?
Prion diseases are neurodegenerative diseases for which there are no treatments, mainly due to our poor understanding of how infectious prions provoke neurodegeneration. We have shown for the first time that prion-induced neurodegeneration depends on a metabolic shift from glucose metabolism to fatty acid metabolism that generates oxidative conditions deleterious for neurons. Normal glucose metabolism can be rescued upon the inhibition of PDK4 kinase by dichloroacetate, which limits neurodegeneration and extends the lifespan of prion-infected animals.
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Why is it important?
This study defines new mechanisms by which infectious prions provoke neurodegeneration. It identifies a new potential therapeutic target against which it is possible to act with an approved drug, dichloroacetate, used to already treat congenital lactic acidosis.
Perspectives
As prion diseases share common neurodegenerative mechanisms with Alzheimer's disease, the deregulation of energetic metabolism would also contribute to neurodegeneration in this disease, and possibly other neurodegenerative diseases with distinct etiologies and clinical manifestations. In the next future, we have to consider if dichloroacetate could be repurposed for treating amyloid-based neurodegenerative diseases.
Benoit Schneider
Centre National de la Recherche Scientifique
Read the Original
This page is a summary of: Loss of prion protein control of glucose metabolism promotes neurodegeneration in model of prion diseases, PLoS Pathogens, October 2021, PLOS,
DOI: 10.1371/journal.ppat.1009991.
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