Researchers have found that excess levels of calcium in brain cells may lead to the formation of toxic clusters that are the hallmark of Parkinson’s disease. This is the first time it’s been shown that calcium influences the way alpha-synuclein behaves.
The study, published in Nature Communications, found that calcium can mediate the interaction between small membranous structures inside nerve endings, which are important for neuronal signalling in the brain, and alpha-synuclein, the protein associated with Parkinson’s disease. Excess levels of either calcium or alpha-synuclein may be what starts the chain reaction that leads to the death of brain cells.
Curiously, it hasn’t been clear until now what alpha-synuclein actually does in the cell: why it’s there and what it’s meant to do. Thanks to super-resolution microscopy techniques, it is now possible to look inside cells to observe the behaviour of alpha-synuclein. To do so, the researchers isolated synaptic vesicles, part of the nerve cells that store the neurotransmitters that send signals from one nerve cell to another.
In neurons, calcium plays a role in the release of neurotransmitters. The researchers observed that when calcium levels in the nerve cell increase, such as upon neuronal signalling, the alpha-synuclein binds to synaptic vesicles at multiple points causing the vesicles to come together. This may indicate that the normal role of alpha-synuclein is to help the chemical transmission of information across nerve cells.
Understanding the role of alpha-synuclein in physiological or pathological processes may aid in the development of new treatments for Parkinson’s disease. One possibility is that drug candidates developed to block calcium, for use in heart disease for instance, might also have potential against Parkinson’s disease, the researchers said.
Article: “C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction”
Reprinted from materials provided by Cambridge University.