How to tackle toxic protein aggregates in Parkinson’s disease

pParkisons Diseasep

Toxicity in the fly’s eye provides clues for how to tackle Parkinson’s disease.

In Parkinson’s disease, misfolded proteins such as α-synuclein accumulate in neuronal inclusions termed Lewy bodies. George Tofaris’s team from the University of Oxford Clinical Neuroscience Department and Benedikt Kessler from the TDI investigated the role of α-synuclein handling and the death of neurons that represents a hallmark of Parkinson’s disease.

The researchers used a fly model and tested the effect of elevated presence of α-synuclein in the eye. Interestingly, they observed that removal of the gene called Usp8 in the fly’s eye reduced α-synuclein levels and associated eye toxicity (illustration). Usp8 is a protease that cleaves ubiquitin, a small protein that can be “tagged” to protein substrates such as α-synuclein.

When Usp8 protease function is removed, it can correct defects due to α-synuclein accumulation, similar to what is observed in neurons affected in Parkinson’s disease. This discovery suggests a novel route to develop drugs for the treatment of this brain disease.

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