14.04.2024

AI and Parkin_s disease

AI helps to analyze the descriptions of chemicals to identify potential new pharma candidates.

Scientists suggest that the language used by researchers, while describing their results can be used to unleash new treatments for Parkin’s disease. They claim that the AI might be able to find an existing anti-cholesterol drug that can improve the use of mitochondria, responsible for energy manufacturing and is affected in Parkinson’s disease.

Unfortunately, the complete way to Parkinson’s disease is a mystery, but it’s clear that mitochondrial dysfunction and the inability to get rid of defective mitochondria are integral parts of that. Five genes, involved in PD are connected to impaired mitophagy one way or another. The authors need compounds that could better the mitophagy process (getting rid of defective mitochondria).

Few of those compounds have been identified. Unfortunately, they harm cells. The authors started searching for known enhancers. 

AI program, IBM Watson for Drug Discovery, helped to analyze keywords, phrases and links. That way semantic “fingerprint” of effective mitophagy enhancers was established. Similar fingerprints have been looked up in the literature on a set of over three thousand candidates from a drug database. .

The top 80 candidates were looked at in cell culture against mitochondrial harm. Top candidates then were tested on several mitophagy assays, that found probucol, to be effective and probably safe. Probucol also appeared to enhance motor function, survival and neuron loss in a few models of Parkonso’s disease.

For probucol to be effective, lipid droplets need to be formatted. Probucol typically aims for ABCA1, which  is probably a mediator for lipid droplets in mitopgahy.

“Our research indicated a duality in methodology of silico and cell-based screening, that showcased already-known and new mechanisms, causing mitophagy improvement”, said McQuibban. Considering the link between lipid droplet accumulation and ABCA1, probucol looks like improving mitophagy through mobilization of lipid droplets, and this is interesting. AI platform was used for the identification of currently approved drugs to be repurposed as treatment of Parkon’s disease.

Yasmin Anderson

AI Catalog's chief editor

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