Researchers find new cause of Parkinson’s disease

The neurodegeneration associated with early-onset Parkinson’s disease has traditionally been blamed on defective or failing mitochondria, a cell’s power factory. But a new discovery now points to the endoplasmic reticulum (ER), a maze-like structure nearby that packages proteins for use by the cell.

The ER’s job is to “fold” proteins, prepping them for use as an energy source for the mitochondria. If the ER doesn’t fold the proteins correctly, the body interprets the proteins as foreign objects and shuts down production, leaving the mitochondria with no way to produce energy, starving the cell. In other words, it's not the power factory that's broken, as previously thought—it's the factory supplier.

Parkinson’s-related neurodegeneration seems to be linked to stress on the ER and its ability to fold proteins correctly rather than on a general failure of the mitochondria, say researchers from the University of Leicester MRC Toxicology Unit. Studies on fruit flies, a common genetic model for human research, showed that flies with stressed and mutated ER had fewer dopaminergic neurons, weaker muscles and slower movement.

That discovery could have great impact on the development of future Parkinson’s treatments, since the cellular stressors that cause the ER to stop producing proteins can apparently be blocked. Researchers used chemicals to reverse the effects of the ER stressors, which raised the number of neurons and improved muscle function.

“This research challenges the current held belief the Parkinson’s disease is a result of malfunctioning mitochondria,” said Dr. Miguel Martins, lead researcher, in a university press release. By identifying and preventing ER stress in a model of the disease it was possible for us to prevent neurodegeneration. Lab experiments, like this, allow us to see what effect ER stress has on Parkinson’s disease. While the finding so far only applies to fruit flies, we believe further research could find that a similar intervention in people might help treat certain forms of Parkinson’s.”


Topics: Clinical