IBM's supercomputer found a hidden new Parkinson's drug.
- Researchers used artificial intelligence to identify Probucol, an existing anti-cholesterol medicine
- It increases mitochondrial waste and is a viable novel therapy for the treatment of Parkinson's disease
- The artificial intelligence software used was from IBM
Drug in Test
Many similar compounds have been found; however, the majority of them cause cell damage, ruling them out as therapeutic options. This prompted the scientists to wonder if the literature describing these compounds could lead them to other compounds, ones that had not previously been connected to mitophagy enhancement but were characterized using phrases that also appeared in articles discussing the known enhancers.The researchers utilized the algorithm to create a semantic "fingerprint" of genuine mitophagy enhancers, and then searched the literature for similar fingerprints on a collection of over three thousand candidates from a pharmacological database.
In cell culture, the top 79 candidates were tested against a mitochondrial toxin. The top three choices from that assay were then examined on multiple different mitophagy assays, and probucol, a cholesterol-lowering medication, was found to have the best combination of effectiveness and likely safety.
In two separate animal models of Parkinson's disease (PD), probucol was reported to enhance motor function, survival, and neuron loss (PD is primarily a movement disorder).
The effect of probucol on mitophagy was dependent on the production and function of lipid droplets, which are transient cell structures that help maintain mitochondrial integrity during stress and accumulate abnormally in Parkinson's disease.
Mystery Around Probucol
Probucol is known to target ABCA1, a lipid transport protein, and lowering ABCA1 levels lowered Probucol's ability to induce mitophagy, implying that ABCA1 is a plausible mediator of the involvement of lipid droplets in mitophagy (1✔ ✔Trusted SourceProbucol: pharmacology and clinical application
Go to source).
"Given the linkage between lipid droplet accumulation and ABCA1, it seems likely that Probucol enhances mitophagy through mobilization of lipid droplets. Targeting this mechanism may be advantageous."
Reference:
- Probucol: pharmacology and clinical application - (https://pubmed.ncbi.nlm.nih.gov/2406299/)
Source-Medindia