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Tofaris group
Parkinson's disease affects more than 10 million people worldwide. The disease is characterised by the build-up of abnormal clumps of the protein alpha-synuclein inside brain cells, but scientists have long struggled to understand exactly how these toxic forms of the protein cause neurons to malfunction and eventually die.
Researchers from the Tofaris lab, part of the Nuffield Department of Clinical Neurosciences and based in the Kavli Institute for Nanoscience Discovery combined advanced molecular analyses of human stem cell models of Parkinson's disease with studies of post-mortem brain tissue from people with Parkinson's disease to investigate the earliest stages of the disease process.
The researchers found that toxic forms of alpha-synuclein bind to a protein called Sec61A, blocking part of a molecular "gateway" that helps newly made proteins enter the cell's protein-processing centre, known as the endoplasmic reticulum.
Blocking this gateway did not activate the classical cellular stress response normally associated with damage to the endoplasmic reticulum. Instead, neurons activated an alternative quality-control pathway, known as UFMylation, suggesting that this represents a previously unrecognised early event in Parkinson's disease.
Read the full story on the Nuffield Department of Clinical Neurosciences website.