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New publication looking at the mechanisms of neuronal damage in Parkinson's disease

posted Jun 12, 2018, 2:07 AM by Mathew Horrocks
There are many different species of alpha-synuclein, and it's therefore a challenge to know which one is a good biomarker or therapeutic target. Using highly resolved methods to study these at the nanoscale, we have helped demonstrate which form of alpha-synuclein is damaging to cells. To achieve this, we brought together a team from multiple disciplines, across different universities and a number of UK DRI centres. Harnessing the breakthroughs in single-molecule methods, single cell imaging and stem cell biology, we have been able to take a multifaceted approach to resolve a significant problem in neurodegeneration.

The study, published in Nature Communications, adds to our growing understanding of the causes of Parkinson’s and other neurodegenerative diseases, and could influence drug design in the future.

We found that in neurons, clumps of alpha-synuclein moved to and damaged key proteins on the surface of mitochondria - the energy powerhouses of cells - making them less efficient at generating energy. They also triggered a channel on the surface of mitochondria to open, causing them to swell and burst, leaking out chemicals that tell the cell to die.

These findings were replicated in human brain cells, generated from skin cells of patients with a mutation in the alpha-synuclein gene, which causes early-onset Parkinson’s disease. By turning patient skin cells into stem cells, we could chemically guide them into become brain cells that could be studied in the lab. This cutting-edge technique provides a valuable insight into the earliest stages of neurodegeneration - something that brain scans and post-mortem analysis cannot capture.