Sunday , November 29 2020

The new discovery confirms the central importance of PINK1-Parkin in patients with Parkinson's disease



Researchers at the Helsinki University Medical School make an unexpected and vital contribution to an international collaborative effort in research into Parkinson's disease.

An international team of scientists, headed by the University of Dundee, UK, has confirmed that a molecular course that has been studied for years under laboratory conditions is also disrupted in patients with Parkinson's disease.

Parkinson's disease is an undesirable neurodegenerative disorder for which there is no cure today. Mutations in two genes called PINK1 and Parkin are related to early forms of Parkinson's. These genes encode discrete enzymes that are predicted to play a central role in protecting the brain from stress.

Previous work has shown that PINK1 works by detecting damage to the cellular "electric grid" and prevents further damage by activating a critical "molecular switch" at Parkin called Serine 65. This finding, published in 2012, was the Professor's workshop Mirka Muqit FRCP, Wellcome Trust Senior Clinical Partner at MRC Protein Phosphorylation Unit & Ubiquitolysis at the University of Dundee, United Kingdom. Although it remains the most mentioned study in Open Biology, the significance of this "molecular shift" in patients with Parkinson's disease remained unclear.

To further understand his significance, Muqit developed a genetically modified mouse to study the Parkin switch on the tissues, but the researchers did not know its importance to humans. The ambitious project was the spearhead Tom McWilliams, who recently moved to Finland as Assistant Professor at the Academy of Sciences of the Helsinki University Medical School. It is noteworthy that through a collaboration involving Professor Anu Suomalainen-Wartiovaara Professor Pentti Tienari and Risto Pohjolan-Pirhonen in the Molecular Neurology program at Helsinki University, a Finnish patient was also identified as being mutated to the same Serine 65 switch .

Impressively, both the mouse and the patient do not have the ability of PINK1 to activate the Parkin enzyme. Thanks to the study of the Parkinson's Progressive Study Initiative, co-ordinated by the Michael J. Fox Foundation, a second patient was found in the United States. This discovery confirms the central importance of PINK1-Parkin in patients with Parkinson's disease and may prove to be crucial for therapeutic development efforts in this area.

Observing the discovery, McWilliams says, "It was very pleasant to see that discovery-based discoveries may be so unexpected in Parkinson's patients. The Helsinki team has made a significant contribution to this work, and thanks to their co-operative spirit and expertise, we have been able to make rapid progress in this area. It would be interesting to identify the mitosis-independent roles of this path in vivo. "

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