Lisa V tries to keep it simple and explains the deal with alpha-synuclein. Originally published online a couple of years ago when a-SYN was still new to the PD community, this article has been updated in the light of more recent research. All evidence from then and now points to this sticky substance being the cause of Parkinson’s. Let’s gets a couple of abbreviations and definitions out of the way first: a-SYN is Alpha-Synucein. PD is Parkinson’s (if you couldn’t work that one out, you’re really in trouble). Aggregates are basically debris or detritus; organic matter produced by the decomposition of organisms. Alpha-Synuclein is a sticky protein found throughout the body, but the motherlode is in the brain. Ideally, the a-SYN protein appears to function in the loading of vesicles; small spherical bits of membrane that carry neurotransmitter molecules to the pre-synaptic end of a neuron. This, in turn, bumps into the business end of another neuron, allowing for the neurotransmitters in the vesicles to be released into the synapse. The top is the presynaptic neuron; the bottom, postsynaptic. They are both separate neurons in this relay event, passing the baton. In Parkinson’s and otherspecific neurodegenerative diseases, it’s been found that a-SYN proteins are ‘misfolding’, creating clumps or aggregates. Like almost all proteins, after a-SYN is synthesised by the cellular machinery (i.e. ribosomes – they build long chains of amino acids, one at a time – exhausting!), it is supposed to fold in a certain way; the entire function of a-SYN is dependent on proper folding. If the folding goes wrong; the protein fails to function. The fall-out of this wayward behaviour is aggregation – crap everywhere that ‘gums up’ the works.