Proteins are the brain’s quiet workers, building, repairing, and keeping systems running so we can move, think, and feel. Most of the time, they do this unnoticed. But occasionally, a protein stops behaving as it should.
One such protein is alpha-synuclein. Under normal conditions, it helps brain cells communicate, particularly at synapses—the tiny gaps where chemical messages are passed. It plays a key role in regulating neurotransmitters like dopamine, which is essential for smooth, coordinated movement.
Alpha-synuclein is unusual because it doesn’t have a fixed shape. It is intrinsically disordered and highly flexible. This makes it effective at its job, but also more vulnerable to misfolding, especially when brain cells are under stress from ageing, inflammation, or injury.
When alpha-synuclein misfolds, it becomes sticky. Instead of moving freely, it begins to clump together, forming larger deposits known as Lewy bodies. These are a defining feature of both Parkinson’s disease and Dementia with Lewy bodies.
Misfolded alpha-synuclein disrupts brain cells in several ways. It interferes with mitochondria, reducing energy production and increasing cellular stress. It overwhelms the cell’s ability to clear damaged proteins. It disrupts communication between neurons, impairing movement and cognition. It also triggers inflammation, as the brain’s immune system responds to the abnormal protein.
Over time, these combined effects lead to cell dysfunction and death.
Symptoms depend largely on where the protein accumulates. In Parkinson’s disease, early damage occurs in the substantia nigra, a region responsible for producing dopamine. As these cells are lost, movement becomes slower and more rigid, often accompanied by tremor and balance difficulties.
In Dementia with Lewy bodies, alpha-synuclein spreads more widely into areas involved in thinking and perception. This leads to fluctuating attention, visual hallucinations, and progressive cognitive decline.
The underlying problem is the same; the difference lies in distribution.
Understanding how alpha-synuclein misfolds and spreads is central to advancing earlier diagnosis, developing biomarkers, and creating treatments that may slow or even halt disease progression.