Parkinson’s disease is a neurodegenerative disorder characterized most notably by motor impairments: shaking, trouble walking, and an overall slowing of movement. While there is no cure for Parkinson’s yet, a team of researchers from the University of Cambridge has taken a big step towards understanding the underlying mechanisms behind the disease’s progression.
Image Source: Visuals Unlimited, Inc/Carol & Mike Werner
Alpha-synuclein (α-syn) is a protein found in the brain that helps facilitate communication between neurons via neurotransmitters, chemical signals sent from neuron to neuron, as seen in the figure above. One of the hallmarks of Parkinson’s disease is the aggregation of α-syn into clumps that are toxic to the surrounding cells, impairing cell communication and ultimately resulting in cell death. The malfunction of the α-syn may also account for the death of cells that produce dopamine, a neurotransmitter that plays a key role in the motor functions of the body.
By closely examining the interactions between α-syn and the surrounding cell membrane lipids and vesicles in the brain, researchers were able to show that the process that may lead to the clumping of α-syn depends heavily on the specific number of α-syn protein and synaptic vesicles, which carry neurotransmitters between neurons. Under normal conditions, α-syn functions in helping the vesicles release the neurotransmitters they are carrying. It attaches to the surface of the vesicle and folds into a different shape to facilitate the transferring of neurotransmitters to a neuron.
Image Source: Visuals Unlimited/Carol & Mike Werner
Studying this process in the laboratory, the researchers determined that when the ratio of α-syn to vesicles is greater than about 10 to 1, the α-syn become too clumped together; they would misfold and group together, forming large toxic structures called Lewy Bodies. These aggregations and their formation can be seen in the figure above. Above this specific threshold level of α-syn, the chance of α-syn aggregating into toxic structures is a thousand times higher than below the threshold level. This beginning of the aggregation of α-syn is called a nucleation event.
This research sheds light on the cellular conditions and initial steps that may lead to the clumping of α-syn, and the subsequent beginnings of neurodegenerative disease. Further understanding of the mechanisms of neurodegenerative disease provide hope that treatments for diseases like Parkinson’s disease are within our reach.
Feature Image Source: Feet in the Creek! by OakleyOriginals
