Scientists have found how a poisonous protein drains mind vitality in Parkinson’s and how one can cease it.
Roughly 1 million individuals in the US live with Parkinson’s illness, and about 90,000 new instances are recognized annually, in response to the Parkinson’s Basis. The situation is a progressive mind dysfunction that slowly destroys cells liable for producing dopamine, a chemical essential for controlled and coordinated movement.
Most existing treatments focus on easing symptoms, but their effects tend to be temporary. Researchers at Case Western Reserve University have now identified a specific biological pathway that appears to contribute directly to the disease itself.
A Closer Look at Protein Damage in the Brain
The team’s findings, recently published in Molecular Neurodegeneration, describe how the buildup of toxic proteins inside brain cells leads to the death of neurons that control movement, a defining feature of Parkinson’s disease.
“We’ve uncovered a harmful interaction between proteins that damages the brain’s cellular powerhouses, called mitochondria,” said Xin Qi, the study’s senior author and Jeanette M. and Joseph S. Silber Professor of Brain Sciences at the Case Western Reserve School of Medicine. “More importantly, we’ve developed a targeted approach that can block this interaction and restore healthy brain cell function.”
After three years of study, the researchers found that alpha-synuclein, a protein closely linked to Parkinson’s disease, forms an abnormal connection with an enzyme called ClpP. This enzyme normally helps maintain healthy cell function, but the interaction disrupts its role.
How Energy Failure Drives Neurodegeneration
When alpha-synuclein interferes with ClpP, the mitochondria suffer damage. Because mitochondria supply energy to cells, their failure leads to widespread neuron loss and neurodegeneration. Experiments in several research models showed that this harmful interaction also speeds up the progression of Parkinson’s disease.
A Decoy Strategy to Protect Brain Cells
To interrupt this destructive process, the research team developed a treatment known as CS2. The compound is designed to block the damaging protein interaction and help mitochondria return to normal function. CS2 acts as a decoy by binding to alpha-synuclein and preventing it from attacking the cell’s energy systems.
In a range of experimental models, including human brain tissue, patient-derived neurons, and mouse models, CS2 reduced brain inflammation and improved both movement and cognitive performance.
Targeting the Root Cause of Parkinson’s
“This represents a fundamentally new approach to treating Parkinson’s disease,” said Di Hu, research scientist in the School of Medicine’s Department of Physiology and Biophysics. “Instead of just treating the symptoms, we’re targeting one of the root causes of the disease itself.”
The discovery was supported by Case Western Reserve’s long history of interdisciplinary collaboration, deep expertise in mitochondrial biology and neurodegenerative disorders, access to advanced disease-relevant models and a proven ability to turn basic science into potential therapies.
Next Steps Toward Human Trials
Over the next five years, the researchers aim to move the treatment closer to clinical testing. Their plans include refining the therapy for use in people, expanding safety and effectiveness studies, identifying key molecular biomarkers linked to disease progression, and advancing the work toward clinical application.
“One day,” Qi said, “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.”
Reference: “Disrupting α-Synuclein–ClpP interaction restores mitochondrial function and attenuates neuropathology in Parkinson’s disease models” by Di Hu, Xiaoyan Sun and Xin Qi, 22 December 2025, Molecular Neurodegeneration.
DOI: 10.1186/s13024-025-00918-w
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