A glitch in the mechanism by which cells recycle damaged components may trigger Parkinson's disease, according to a study by scientists at the Albert Einstein College of Medicine of Yeshiva University.
The research, which appears in the January 2 advance online issue of The Journal of Clinical Investigation, could lead to new strategies for treating Parkinson's and other neurodegenerative diseases.
All cells depend on a surveillance system known as autophagy (which literally means “self eating”) to digest and recycle the damaged molecules that arise as cells age. In autophagy, defective proteins and other molecules are transported to membrane-bound sacs called lysosomes. After attaching to the lysosomal membrane, the molecules enter the lysosome, where they are digested by enzymes. This cleanup process may be particularly important for nerve cells, which generate defective molecules more rapidly than most other types of cells. When autophagy is impaired, toxic compounds can accumulate and cause cell death.
“It is widely suspected that accumulation of a particular protein, known as alpha-synuclein, within affected nerve cells of Parkinson's disease patients contributes to the death of these cells,” says Dr. Ana Maria Cuervo, senior author of the article and associate professor of anatomy & structural biology at Einstein.
Dr. Cuervo previously showed that mutant forms of alpha-synuclein—found in the five to 10 percent of patients who have familial Parkinson's disease—are poorly digested via autophagy and also block the breakdown of other substances. While these alpha-synuclein mutations are rare, other modifications of alpha-synuclein—phosphorylated and oxidized forms, for example—can be found in the brains of all Parkinson's disease patients.