Proteins And Parkinson’s

A common problem underlying many neurodegenerative diseases such as ALS, Alzheimer’s disease, and Parkinson’s disease is an abnormal accumulation of proteins in neurons.

In Parkinson’s the protein alpha-synuclein (pictured below) builds up in large masses called Lewy bodies. These bodies are toxic to the cell and can lead to cell death seen in Parkinson’s disease.

Parkinson’s Disease was first described by Dr. James Parkinson in 1817. The gene PARK encodes for the protein parkin (appropriately named after Dr. Parkinson). Parkin is a component of a clean-up system of the cell called the Ubiquitin Proteasome System or UPS (basically a fancy name for the garbage man of the cell). When a protein has an error or isn’t functioning properly, it is marked for death and the UPS system comes around to destroy it.  But because parkin is involved in this mechanism, it is not working properly in patients with Parkinson’s which allows the buildup of proteins leading to cell death.

(a proteasome chewing up a purple protein)

The current treatment for Parkinson’s disease is the drug L-DOPA which only deals with side effects of the disease and not the underlying protein build up. Parkinson’s specifically affects dopaminergic cells so they are not able to release sufficient amount of dopamine. Treatment with L-DOPA can help increase levels of dopamine in these patients and improve quality of life.

While there are many other molecular pathways thought to be involved in the progression of Parkinson’s this main concept of protein buildup is similar to that of other diseases. If we want to combat these neurodegenerative diseases, we can look into boosting our cells UPS system which naturally fights protein aggregation. In relation to Parkinson’s research, there are promising trials for drugs that will target and inhibit certain steps in the pathogenesis of Parkinson’s Disease specifically.

Michael J. Fox has started a foundation dedicated to finding the cure for Parkinson’s. He was diagnosed in 1991, and has been a large advocate for funding research since he released the statement of his diagnosis. They have raised $700 million for research programs for Parkinson’s.