New Findings about Protein Aggregation and Chaperones May Help Limit Neuronal Damage

Two new collaborative studies between Chris Dobson, Tuomas Knowles and Michele Vendruscolo’s research groups at the University of Cambridge, UK, shed light on how to potentially limit damage to neurons caused by misfolded proteins. In the first study, published May 9 in Proceedings of the National Academy of Sciences online, the researchers performed in vitro aggregation assays using seed a-synuclein amyloid fibrils and found that the rate of secondary nucleation of these seed fibrils is greatly accelerated under acidic conditions. At pH values below 6, which are found in some intracellular organelles such as endosomes, the balance is shifted toward nucleation and protein aggregation. These findings shed light on mechanisms of protein aggregation and spread in Parkinson’s disease, but also have implications for other protein misfolding diseases such as Alzheimer’s disease and ALS. A second study, published May 20 in PNAS from Chris Dobson’s laboratory, demonstrates an approach for improving effectiveness of molecular chaperones, the enzymes that ensure correct folding of proteins. When a chaperone called a2-macroglobulin (a2M) comes into contact with the oxidant hypochlorite, it becomes much more effective at ensuring that amyloid-b peptide folds correctly. These finding may ultimately help identify avenue to improve chaperone function and accelerate clearance of neurotoxic misfolded proteins. Click here to read more about these findings.

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