Cellular switch discovery offers hope for Parkinson's treatment
Scientists have identified a key cellular regulator called PP2A-B55alpha that balances mitochondrial health, potentially leading to new therapies for Parkinson's disease. In preclinical models, reducing its activity improved motor symptoms and mitochondrial function. The findings, published in Science Advances, could extend to other mitochondrial disorders and cancer.
Mitochondria, the cell's energy producers, maintain a delicate balance between removing damaged organelles through mitophagy and generating new ones via biogenesis. Disruptions in this process contribute to diseases like Parkinson's, where the loss of mitochondria leads to the death of dopaminergic neurons.
Researchers from Università Cattolica in Rome and Roma Tre University discovered that phosphatase B55 (PP2A-B55alpha) plays a central role in this regulation. "On the one hand," Professor Francesco Cecconi explains, "it promotes the removal of damaged mitochondria by stimulating mitophagy, a selective process for removing inefficient and potentially dangerous organelles. On the other, B55 acts as a controller of mitochondrial biogenesis, stabilizing the main promoter of new mitochondrial formation."
This dual function depends on B55's interaction with Parkin, a protein implicated in Parkinson's mitophagy mechanisms. In animal models using Drosophila fruit flies, reducing B55 levels improved motor defects and mitochondrial alterations typical of the disease, an effect requiring Parkin's presence and primarily targeting biogenesis.
The study, led by Cecconi and conducted by Valentina Cianfanelli, was published in Science Advances on October 4, 2025 (volume 11, issue 40; DOI: 10.1126/sciadv.adw7376). It suggests developing small molecules that penetrate the brain to target B55 in dopaminergic neurons, potentially counteracting cell death. Professor Cecconi notes broader applications: a 'universal' drug modulating B55 could treat mitochondrial myopathies, neurodegenerative diseases, and even enhance cancer therapies by disrupting tumor cell plasticity.
Future research will focus on identifying safe molecules and strategies in preclinical and human models to modulate B55 for these conditions.