Small molecule may block protein buildup in neurodegenerative diseases

A team of researchers from NYU Abu Dhabi and the University of Denver have identified a promising small molecule that could help slow or halt the progression of serious brain diseases such as Parkinson's disease, offering new hope for treatments that go beyond managing symptoms.

These diseases, which also include Lewy body dementia and multiple system atrophy, are caused by aggregation and spread of a neuronal protein, which damages brain cells over time. Currently, there are no approved treatments that can stop or slow this process.

In the new study published in Science Translational Medicine, the Magzoub lab at NYU Abu Dhabi and the Kumar lab at the University of Denver, along with international collaborators, developed a special type of small molecule designed to block this harmful buildup. The molecule, known as SK-129, works by preventing the protein from clumping together and spreading in the brain.

The team tested SK-129 across a wide range of disease models, including human cells, patient-derived tissue, and living organisms. In all cases, the molecule reduced the harmful effects linked to the disease.

Importantly, the researchers also showed that SK-129 can cross the blood-brain barrier, a protective layer that often prevents drugs from reaching the brain. In mouse models, the molecule significantly reduced the development of disease-related damage in the brain.

"This is an important step toward developing treatments that target the root cause of these diseases," said NYU Abu Dhabi Associate Professor of Biology and co-lead author Mazin Magzoub. "Instead of only treating symptoms, we are working toward slowing or stopping the disease itself."

Another key finding is that the molecule can also block the harmful interaction with another neuronal protein that is strongly linked to Alzheimer's disease. This dual action could make it especially powerful in tackling complex neurological conditions.

While more research is needed before clinical use, the findings represent a major step forward in the search for effective treatments for these currently incurable diseases.