Parkinson’s and alpha-synuclein

What is alpha-synuclein?

Alpha-synuclein is a protein that is extremely abundant in our brains, making up around 1% of all the proteins floating around in each nerve cell or neuron (the main types of cell in the brain). Proteins make up most of the biological pathways that are going on inside each neuron, and allow our brains to work. In order for each protein to function properly, they must be manufactured correctly.

In healthy neurons, correctly constructed alpha-synuclein is typically found just inside the surface of the neuron membrane as well as in the tips of the branches extending out from the neurons – in structures called presynaptic terminals which are critical to passing the chemical messages between each neuron.

Why is alpha-synuclein relevant to Parkinson’s?

Five genetic mutations in the alpha-synuclein gene have been identified as an associated increased risk of Parkinson’s and these account for 10-20% of people affected by Parkinson’s. So, from a genetic perspective, alpha-synuclein is associated with Parkinson’s; but it is also associated at a protein level.

In the brains of many people with Parkinson’s, some alpha-synuclein protein has been found to be folded in a disordered way. These incorrectly constructed versions of alpha-synuclein clump together in aggregates that are called ‘Lewy bodies’. Lewy bodies are circular clumps of alpha-synuclein (and other proteins) that are found in the brains of people with Parkinson’s. They are abundant in areas of the brain that have suffered cell loss, such as the region of the brain containing neurons that produce dopamine – the hormone which controls feelings of pleasure, satisfaction and motivation; also movement, memory, mood, sleep, learning, concentration, and other body functions.

Alpha-synuclein and Lewy Body forms

We don’t know what causes Lewy bodies to form but there is a lot of evidence supporting the idea that alpha-synuclein is passed between neurons. Once inside, the alpha-synuclein ‘seeds’ the formation of new Lewy bodies inside the next neuron, and this is how the disease is believed to progress.

Can we stop alpha-synuclein clumping, and Lewy bodies from developing and spreading?

This is a very interesting question and one which is being asked and investigated by researchers around the world.

One area of research is that of vaccines that target alpha-synuclein; the idea is that these vaccines will capture and remove the alpha-synuclein being passed between cells and thus stop or at least slow down Parkinson’s progression.

Other areas of research are focused on medicines that inhibit the formation of alpha-synuclein clumps.

An area of research Cure Parkinson’s is involved in is that of the medicine, ambroxol, which has shown to improve the waste clearance from cells, including the mis-folded alpha-synuclein.