Aggregation of Alpha-synuclein and its role in Parkinson’s Disease
There are many factors that lead to the onset of Parkinson’s disease. Many of you may have heard of the genetic factors such mutations in genes PARK1 and PARK2 that can be inherited from parents while others know more about the risk of bacterial or viral infections that may lead to Parkinson’s disease-like symptoms. Today we are going to talk about a lesser-known factor that has become a target in the study of Parkinson’s disease treatments.
Scientists have discovered that in the brains of roughly 20% of Parkinson’s disease patients, there is a large increase of a molecule known as alpha-synuclein.
Alpha-synuclein is a small molecule encoded by the SNCA gene and is located primarily in the brain. Its current function is being debated, although many have agreed that it plays a role in intracellular trafficking in the cell. Under regular physiological conditions, alpha-synuclein acts independently as it associates with the membrane of organelles in the cell. However, various conditions may lead to its aggregation. One of these conditions is high concentration of fatty acids in the brain. As we age, the amount of fatty acids in our brains naturally increase. For some individuals, the amount surpasses an appropriate threshold resulting in different complications of the brain due to faulty interactions and slight increase in acidity. During this time, alpha-synuclein may become confused and will bind these fatty acids that mimic the phospholipids in the membrane. As more alpha-synucleins gather towards the fatty acids they begin to associate with one another and eventually clump together or aggregate. This aggregation of the alpha-synuclein molecule causes concerns as it may progress and become a Lewy body.
Lewy bodies are protein deposits and can be made up of different types of molecules. In dementia patients, their Lewy bodies are made up of molecules known as amyloid-beta while in Parkinson’s disease it is made up of alpha-synucleins. These Lewy bodies then interfere with the dopamine neurons beginning in the basal ganglia.
Current research is looking into new drugs or techniques that can be used to reduce alpha-synuclein aggregation in the brain and inhibit these Lewy body formations thus reducing neurodegeneration. As we continue to progress in our understanding of the pathology of Parkinson disease, we become one step closer to finding a cure.
If you like to know more about this topic, check out this review by the Science of Parkinson’s: https://scienceofparkinsons.com/alpha-synuclein/
Image from: https://www.youtube.com/watch?v=SAxioqRwtcQ