HYPE protein found to target alpha-synuclein

Researchers in the US have identified a protein in the brain that may reduce the spread of the toxic alpha-synuclein protein in Parkinson's.

The research, published in the Journal of Molecular Biology, found that a protein called HYPE may play a role in modifying the alpha-synuclein protein to make it less toxic and less likely to form protein clumps.

A toxic protein

Alpha-synuclein is a protein that was first linked to Parkinson's 20 years ago. It is one of the main proteins found inside the Lewy bodies - sticky bundles of proteins that appear inside the brain cells of everyone with the condition.

This protein is also believed to play a key role in the progression of Parkinson's. In 2017, researchers found that a toxic form of alpha-synuclein was able to puncture cell membranes, killing them and helping to the spread of the Parkinson's pathology across the brain.

Targeting the stress response

In this new study, researchers looked specifically at a protein, called HYPE, which regulates the stress response in cells. We know that when cells are stressed, proteins can become misfolded, increasing the chance of them clumping together and becoming toxic.

As alpha-synuclein is misfolded in Parkinson's, the researchers looked at whether HYPE, a key regulator of the stress response, could play a role in managing alpha-synuclein.

Slowing the spread?

Using cell models, the researchers showed that HYPE targets alpha-synuclein by adding molecules called adenosine monophosphate (AMP) to it, which was able to reduce the amount of protein clumping.

Next, the team used a model of a cell membrane to show that HYPE-modified alpha-synuclein was less able to puncture cell membranes, compared with toxic alpha-synuclein. This offers hope that HYPE could help slow the spread of Parkinson's across the brain.

Dr Lynn Duffy, Senior Science Content Writer at Parkinson's UK, says:

“This is early research, done in cells, so we have a long way to go before we can translate these findings into a drug that can be used by people living with Parkinson's.

“But reducing the toxic nature of alpha-synuclein is one of the most hopeful routes to new treatments that can slow or stop Parkinson's.”

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