Researchers discover enzyme that protects brain from Parkinson’s
Scientists have identified an enzyme that protects brain cells from Parkinson’s disease by regulating how mitochondria — the cell’s energy producers — are recycled and replaced.
The protein complex, known as PP2A-B55α, acts as a molecular switch that determines whether cells repair or create mitochondria, maintaining the energy balance vital for neuron survival.
Mitochondria are the cell’s powerhouses that generate energy.
When they become damaged and aren’t properly replaced, nerve cells begin to fail — a process central to Parkinson’s and other neurodegenerative diseases.
Researchers from Roma Tre University and Università Cattolica del Sacro Cuore in Rome made the discovery using human cell cultures and fruit fly models.
The team, led by Valentina Cianfanelli and Francesco Cecconi, found that PP2A-B55α regulates mitochondrial turnover even in normal, non-stressed conditions, helping cells adjust their energy production to neuronal needs.
Previously, scientists had established that proteins called Parkin and PINK1 tag damaged mitochondria for disposal through a process known as mitophagy.
However, it was unclear how cells sensed when to activate repair or to create new mitochondria through a mechanism called mitochondrial biogenesis.
The new research shows PP2A-B55α interacts with the Parkin–PARIS–PGC-1α pathway, which controls new mitochondrial production.
Normally, a protein called PARIS blocks mitochondrial creation by suppressing PGC-1α. When cells need more mitochondria, Parkin removes PARIS, allowing production to resume.
PP2A-B55α modifies PARIS through phosphorylation — a chemical change that determines whether Parkin can remove it.
In fruit flies with mutations in the PINK1 gene, lowering PP2A-B55α levels corrected mitochondrial damage and improved movement.
The flies climbed faster and their mitochondria appeared normal again. However, this repair did not occur when Parkin was missing, confirming PP2A-B55α acts through a Parkin-dependent pathway.
Unexpectedly, reducing B55α levels improved mitochondrial health by stimulating the formation of new mitochondria rather than increasing recycling.
This suggests PP2A-B55α acts as a molecular switch, enabling neurons to maintain the right number of mitochondria.
This regulation prevents neurons from wasting energy producing too many mitochondria or risking damage by producing too few.
In Parkinson’s, the loss of mitochondria leads to the death of dopamine-producing neurons, causing the movement problems typical of the disease.
The findings suggest that inhibiting PP2A-B55α could restore mitochondrial balance and protect these neurons.
When researchers blocked B55α activity in animal models of Parkinson’s, movement improved and mitochondrial function was restored — pointing to potential new treatments to prevent or even reverse neurodegeneration.
The discovery could have wider implications.
Since mitochondrial failure also contributes to muscle diseases and some cancers, adjusting B55α activity could help stabilise energy production across other tissues.
Cecconi said his team is now working to identify small molecules that can selectively alter B55α activity in the brain, with the aim of developing a drug to restore mitochondrial balance in different conditions.
