Calcium May Play a Role in The Development of Parkinson’s Disease

Source: University of Cambridge

Summary: 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.

Parkinson’s disease is one of a number of neurodegenerative diseases caused when naturally occurring proteins fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy bodies, are the sign of Parkinson’s disease. An international team of researchers led by the University of Cambridge 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. The study findings were published in the journal Nature Communications.

Neurodegenerative disease

Tyrosine hydroxylase positive neuron stained with a synaptic marker. Credit: Janin Lautenschläger

According to the charity Parkinson’s UK, one in every 350 adults in the UK – an estimated 145,000 in all – currently has the condition, but as yet it remains incurable. Thanks to super-resolution microscopy techniques, it is now possible to look inside cells to observe the behavior of alpha-synuclein. To do so, the research team and her colleagues isolated synaptic vesicles, part of the nerve cells that store the neurotransmitters which 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.

First author Dr. Janin Lautenschläger said, “This is the first time we’ve seen that calcium influences the way alpha-synuclein interacts with synaptic vesicles”, “We think that alpha-synuclein is almost like a calcium sensor. In the presence of calcium, it changes its structure and how it interacts with its environment, which is likely very important for its normal function.”

More Information: Janin Lautenschläger et al, “C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction”, Nature Communications (2018). DOI: 10.1038/s41467-018-03111-4

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