Parkinson’s Disease: Scientists Find New Target to Destroy Buildup Of Toxic Protein Clumps

What scientists do know is that when alpha-synuclein bears tags of the small protein ubiquitin, enzymes come and carry it away for destruction. The process of marking proteins for clearance using ubiquitin tags is called ubiquitination.

The recent study reveals that USP13 removes the ubiquitin tags on alpha-synuclein. As a result, enzymes do not clear the protein away, and it accumulates to form toxic Lewy bodies.

The researchers showed that blocking USP13 in mouse models of Parkinson’s disease made Lewy bodies disappear and also stopped them from forming again.

This followed the discovery that the postmortem brain tissue of people with Parkinson’s disease contained high levels of USP13.

The team also investigated the relationship between USP13, alpha-synuclein, and another protein that is linked to Parkinson’s disease called parkin.

USP13 stopped parkin from doing its job

Parkin helps direct the breakdown of proteins in cells. It senses ubiquitin tags and targets the tagged protein for degradation. Scientists have identified links between some forms of Parkinson’s disease and “loss of parkin function.”

It appears that, by removing the ubiquitin tags, USP13 prevents parkin from consigning alpha-synuclein to the cell’s waste management process.

Using mouse models of Parkinson’s disease, the team showed that both the tagging and destruction of alpha-synuclein increased when mice were lacking USP13.

There was also less destruction of dopamine cells in these mice and improved motor function.

The researchers now want to develop a USP13 blocker that doctors can use as part of a therapy that targets protein clearance in neurodegenerative diseases, such as Parkinson’s disease.

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