Excess calcium may play a role in development of Parkinson’s

Excessive levels of calcium in brain cells may lead to the formation of toxic clusters that are the hallmark of Parkinson’s disease, according to new research by the University of Cambridge.

The researchers 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, which have been published in the journal Nature Communications, take us a step closer towards understanding how and why people develop Parkinson’s, which is currently 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 deposits of alpha-synuclein, also known as Lewy bodies, are indicative of Parkinson’s disease.

It hasn’t been clear until now what alpha-synuclein actually does in the cell. 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.

Dr. Gabriele Kaminski Schierle, the study’s senior author, said: ‘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.’

Thanks to super-resolution microscopy techniques, it is now possible to look inside cells to observe the behaviour of alpha-synuclein. 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.

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.