A new study shows how the Parkinson’s protein alpha-synuclein harms brain cells by disrupting mitochondria.
Abnormal clumps of alpha-synuclein can injure neurons. Mitochondria are the cell’s energy producers, and their failure starves cells of power.
The work clarifies how these problems connect, pointing to a direct interaction that undermines mitochondrial function.
Researchers from Case Western Reserve University School of Medicine in the US filled in the missing link between the toxic build-up of proteins and the death of critical brain cells.
“We’ve uncovered a harmful interaction between proteins that damages the brain’s cellular powerhouses, called mitochondria,” says neuroscientist Xin Qi.
“More importantly, we’ve developed a targeted approach that can block this interaction and restore healthy brain cell function.”
In lab tests, the team observed interactions between alpha-synuclein and an enzyme called ClpP, which helps manage mitochondrial waste removal.
The results suggest it is the way alpha-synuclein binds to ClpP that disrupts mitochondrial function, producing knock-on effects including a decline in dopamine production. Dopamine is a chemical messenger in the brain.
The research also involved a potential treatment to counter this biochemical reaction. A short length of protein called CS2 was designed to act as a decoy for alpha-synuclein, diverting its attention away from ClpP and cell mitochondria.
In tests on human brain tissue, mouse models and lab-grown neurones, CS2 was shown to have positive effects.
It reduced brain inflammation and restored some motor and cognitive function in animals.
“This represents a fundamentally new approach to treating Parkinson’s disease,” says neurophysiologist Di Hu.
“Instead of just treating the symptoms, we’re targeting one of the root causes of the disease itself.”
Researchers estimate it might be five years until human clinical trials could evaluate CS2’s safety and efficiency in humans.
“One day we hope to develop mitochondria-targeted therapies that will enable people to regain normal function and quality of life, transforming Parkinson’s from a crippling, progressive condition into a manageable or resolved one,” says Qi.
