Too Much Protein may Kill Brain Cells as Parkinson’s Progresses

NIH-funded study on key Parkinson’s gene finds a possible new target for monitoring the disease

Scientists may have discovered how the most common genetic cause of Parkinson’s disease destroys brain cells and devastates many patients worldwide. The study’s results may help scientists develop new therapies.

Parkinson’s killer lurks within NIH-funded scientists show that the deadly Parkinson’s gene LRRK2 can kill nerve cells (green) by tagging the s15 ribosomal protein (purple), a cog in a cell’s protein-making machinery.Courtesy of Dawson lab, JHU Morris K. Udall Center of Excellence for Parkinson’s Disease.

The investigators found that mutations in a gene called leucine-rich repeat kinase 2 (LRRK2; pronounced “lark two” or “lurk two”) may increase the rate at which LRRK2 tags ribosomal proteins, which are key components of protein-making machinery inside cells. This could cause the machinery to manufacture too many proteins, leading to cell death.

“For nearly a decade, scientists have been trying to figure out how mutations in LRRK2 cause Parkinson’s disease,” said Margaret Sutherland, Ph.D., a program director at NINDS. “This study represents a clear link between LRRK2 and a pathogenic mechanism linked to Parkinson’s disease.”

Affecting more than half a million people in the United States, Parkinson’s disease is a degenerative disorder that attacks nerve cells in many parts of the nervous system, most notably in a brain region called the substantia nigra, which releases dopamine, a chemical messenger important for movement. Initially, Parkinson’s disease causes uncontrolled movements; including trembling of the hands, arms, or legs. As the disease gradually worsens, patients lose ability to walk, talk or complete simple tasks.

“Our results support the idea that changes in the way cells make proteins might be a common cause of Parkinson’s disease and possibly other neurodegenerative disorders,” said Dr. Dawson.