This is the first time we’ve seen that calcium influences the way alpha-synuclein behaves.
- Janin Lautenschlӓger
The international team, 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 findings, reported in the journal Nature Communications, represent another step towards understanding how and why people develop Parkinson’s. 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.
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.
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. It is implicated in various processes, such as the smooth flow of chemical signals in the brain and the movement of molecules in and out of nerve endings, but exactly how it behaves is unclear.
“Alpha-synuclein is a very small protein with very little structure, and it needs to interact with other proteins or structures in order to become functional, which has made it difficult to study,” said senior author Dr Gabriele Kaminski Schierle from Cambridge’s Department of Chemical Engineering and Biotechnology.
Thanks to super-resolution microscopy techniques, it is now possible to look inside cells to observe the behaviour of alpha-synuclein. To do so, Kaminski Schierle and her colleagues isolated synaptic vesicles, part of the nerve cells that store the neurotransmitters which send signals from one nerve cell to another.
Image:Tyrosine hydroxylase positive neuron stained with a synaptic marker
Credit: Janin Lautenschlӓger
Reproduced courtesy of the University of Cambridge