The existence of a protein that can prevent Parkinson's disease has been revealed for the first time. For 20 years, this protein has been known to be a potential target for Parkinson's disease treatment, but this is the first time its structure and mechanism have been elucidated.
Researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Australia announced on the 14th that they have captured images for the first time of the PINK1 protein binding to mitochondria and have clarified the principle of removing damaged mitochondria in an international journal, "Science." Mitochondria are organelles that produce energy.
Parkinson's disease is a degenerative brain disorder characterized by the reduction of dopamine neurons that control involuntary muscle movement, leading to tremors in the hands and feet and a shuffling gait. In severe cases, cognitive abilities may decline, leading to dementia. Currently, there are about 10 million patients with Parkinson's disease worldwide, but there is no definitive treatment. Only medications that slow the progression of symptoms are available.
The Australian researchers have revealed for the first time the structure of the PINK1 protein, which is known to be related to Parkinson's disease, enhancing the possibility of fundamental treatment. PINK1 helps remove unnecessary parts and regenerate when mitochondrial function is impaired or damaged. In 2006, it was confirmed that a decline in mitochondrial repair ability leads to Parkinson's disease, but how PINK1 binds to and repairs damaged mitochondria has not been elucidated.
The researchers used cryo-electron microscopy (Cryo-EM) to capture the structure of PINK1 binding to mitochondria for the first time. PINK1 binds with the help of the TOM complex and VDAC2 channel present on the surface of mitochondria. It was also confirmed that when PINK1 binds to mitochondria, it induces substances that break down damaged areas.
Silvi Carrigari, a senior researcher at WEHI, said, "This is the first time we have seen PINK1 bind to damaged mitochondria," adding that "we also confirmed for the first time how mutations in PINK1 affect patients with Parkinson's disease."
When mitochondria are damaged, the electrical signals flowing on their surface change. PINK1 detected these changes in electrical signals and bound to the mitochondria. In contrast, in patients with Parkinson's disease, PINK1 fails to properly read the electrical signals of the mitochondria and cannot remove the damaged areas.
With the clarification of PINK1's mechanism, the development of new drugs for Parkinson's disease is expected to accelerate. David Commander, a professor at WEHI, noted, "Enhancing PINK1's function could be a turning point in changing the lives of patients with Parkinson's disease." Global pharmaceutical companies are already developing Parkinson's disease treatments targeting PINK1.
U.S. pharmaceutical company AbbVie acquired Mitokinin, which was developing a new drug for Parkinson's disease that acts on PINK1, in 2023. Jonathan Sedgewick, AbbVie's senior vice president, explained in a press release at the time, "There are only symptom-relieving treatments for Parkinson's disease; there is no treatment that can stop the progression. A PINK1-targeted therapy could completely change the disease's progression and provide a new approach to helping patients."
U.S. biotechnology company Biogen is also researching Parkinson's disease treatments using PINK1. The research results have been published multiple times in journals. Biogen researchers, in collaboration with McGill University in Canada, also published in September of last year in the international journal "Nature Communications" about finding a molecular adhesive that enhances the activity of the protein Parkin, which is related to PINK1.
References
Science (2025), DOI: https://doi.org/10.1126/science.adu6445
Nature Communications (2024), DOI: https://doi.org/10.1038/s41467-024-51889-3