Ursolic Acid for Neurodegenerative Disease

Ursolic acid, a supplement from Apple peels, rosemary and thyme, is a peristome proliferator- activated receptor gamma that is neuroprotective and increases the metabolism of triglycerides into beta hydroxybutyrate, the ketone body metabolite derived from coconut oil and MCT oil.  This both protects, provides additional alternative brain energy substrate and increases mitochondrial biogenesis or greater metabolic factories for the cell.

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Highlights

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  Mitochondrial dysfunctions contribute to the pathogenesis of Parkinson's disease (PD).
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  PPARγ is a transcription factor with metabolic functions in the body.
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  PGC-1α is a master regulator of mitochondrial biogenesis and cell viability.
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  PPARγ agonist increased PGC-1α and cell respiration in human dopaminergic neurons.
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  PPARγ agonist increased the phosphorylation of CREB and AC6 levels in the neurons.
  
  

http://www.sciencedirect.com/science/article/pii/S0028390815301842

Abstract

Mitochondrial dysfunction has been linked to several neurodegenerative diseases such as Parkinson's disease (PD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master gene for mitochondrial biogenesis and has been shown to be neuroprotective in models of PD. In this work we have studied the mechanisms by which peroxisome proliferator-activated receptor-γ (PPARγ) selective agonist N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-l-tyrosine hydrate (GW1929) acts on human dopaminergic neurons in culture. Data showed that GW1929 increased the viability of human dopaminergic neurons and protected them against oxidative stress induced by H₂O₂ and the mitochondrial toxin Rotenone. The enhanced resilience of the neurons was attributed to increased levels of mitochondrial antioxidants and of PGC-1α. GW1929 treatment further increased cell respiration, mitochondrial biogenesis and sirtuin-1 (SIRT1) expression in the human dopaminergic neurons. Phosphorylation of cAMP responsive element-binding protein (CREB) was also robustly increased in GW1929-treated cells. Together these results show that the PPARγ agonist GW1929 influences CREB signaling and PGC-1α activities in the human dopaminergic neurons contributing to an increased cell viability. This supports the view that drugs acting on the PPARγ-PGC-1α signaling in neurons may have beneficial effects in PD and possible also in other brain disorders.