I wonder if other members have found value in the naturally available ursolic acid. The summary of the report is as follows;
The mitochondrial rescue effect was confirmed for 15 of these 29 compounds inparkin-mutant fibroblasts from additional patients not included in the initial screen. Of 15 compounds, two were chosen for subsequent functional studies, namely ursocholanic acid and the related compound dehydro(11,12)ursolic acid lactone.
Both compounds markedly increased the activity of all four complexes of the mitochondrial respiratory chain. The naturally occurring compound ursolic acid and the licensed drug ursodeoxycholic acid are chemically closely related to ursocholanic acid and dehydro(11,12)ursolic acid lactone. All four substances rescue mitochondrial function to a similar extent in parkin-mutant fibroblasts, suggesting a class effect.
The mitochondrial rescue effect depends on activation of the glucocorticoid receptor with increased phosphorylation of Akt and was confirmed for both ursocholanic acid and ursodeoxycholic acid in a Parkin-deficient neuronal model system. Of note, both ursocholanic acid and ursodeoxycholic acid also rescued mitochondrial function in LRRK2G2019S mutant fibroblasts.
Our study demonstrates the feasibility of undertaking drug screens in Parkinson’s disease patients’ tissue and has identified a group of chemically-related compounds with marked mitochondrial rescue effect. Drug repositioning is considered to be a time- and cost-saving strategy to assess drugs already licensed for a different condition for their neuroprotective effect. We therefore propose both ursolic acid as a naturally occurring compound, and ursodeoxycholic acid as an already licensed drug as promising compounds for future neuroprotective trials in Parkinson’s disease.
Fortunately ursolic acid is available in apple peel and cranberries. Maybe an apple a day will keep the shakes at bay??