Alpha-synuclein interferes with cellular energy and transport

“For many years, failure of energy metabolism was considered a primary event in Parkinson’s. With the emergence of alpha-synuclein as a major player in the disease process, studies on the failure of energy metabolism received less attention. This paper is important because it brings these two disease mechanisms together and appears to provide insight into how they are linked.” Dr. Patrik Brundin

Increasing evidence indicates that problems with cellular powerplants, known as mitochondria, cause a cascade of problems that may contribute to Parkinson’s, including the build-up abnormal alpha-synuclein. This accumulation then further impairs the mitochondria, leading to a vicious cycle that aids in disease progress. However, it was unclear exactly how this relationship worked.

This study shows that a modified version of alpha-synuclein links up with a protein called TOM20, which is responsible for moving molecules into the mitochondria. The connection prevents TOM20 from binding to another protein required to keep transport into the mitochondria working. The result is a breakdown in cellular energy production.

The study found that by overexpressing TOM20 there were beneficial effects on mitochondrial functioning, suggesting this as a potential therapeutic target in Parkinson’s.

Another recent study highlights a different mechanism which supports this idea of a vicious cycle of alpha-synuclein accumulation and impaired mitochondrial functioning aiding the progression of Parkinson’s. In a similar way to the study described above, this study shows that a modified version of alpha-synuclein binds to a protein called VAPB loosening its association to the mitochondria. This also disrupts cellular energy production and can result in damage to neurons.