Nav: Home

A molecular switch links a Scottish mouse, a Finnish patient and Parkinson's disease

November 07, 2018

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

Parkinson's disease is a relentless neurodegenerative disorder for which no cure currently exists. Mutations in two genes called PINK1 and Parkin are associated with early-onset forms of Parkinson's. These genes encode distinct enzymes that are predicted to play a pivotal role in protecting the brain against stress.

Previous work established that PINK1 works by detecting damage to the cellular 'power grid', and prevents further damage by activating a critical "molecular switch" in Parkin called Serine 65. This finding published in 2012 was led by the laboratory of Professor Miratul Muqit FRCP, Wellcome Trust Senior Clinical Fellow at the MRC Protein Phosphorylation & Ubiquitylation Unit at the University of Dundee, UK. Although it remains the most cited study in Open Biology, the importance of this "molecular switch" in Parkinson's patients has remained elusive.

To further understand its importance, Muqit developed a genetically engineered mouse to study the Parkin switch in tissues, but researchers were unaware of its significance in humans. The ambitious project was spearheaded by Tom McWilliams, who recently relocated to Finland as a Tenure Track Assistant Professor and Academy Scientist at the Faculty of Medicine, University of Helsinki. Remarkably, through a collaboration involving Academy Professor Anu Suomalainen-Wartiovaara, Professor Pentti Tienari and Risto Pohjolan-Pirhonen, MD, at Molecular Neurology Programme of University of Helsinki, a Finnish patient was also identified to have a mutation in the same Serine 65 switch.

Strikingly, both the mouse and the patient lack the ability of PINK1 to activate the Parkin enzyme. Thanks to the Progressive Parkinson's Markers Initiative study coordinated by the Michael J. Fox Foundation, a second patient in the United States was identified. This discovery confirms the central importance of the PINK1-Parkin pathway in Parkinson's patients and will likely prove vital for therapeutic development efforts in this area.

Remarking on the discovery, McWilliams says: "It was particularly gratifying to see that findings from discovery-based science can have such unexpected relevance in Parkinson's patients. The Helsinki team made an outstanding contribution to this work, and thanks to their collaborative spirit and expertise, we were able to make rapid progress in this area. It will be interesting to determine the mitophagy-independent roles of this pathway in vivo."
-end-
The research is published today as the cover article of Open Biology, an open access of the Royal Society.

The study also involved collaborations with leading groups at Cardiff University, CNRS INSERM, Paris and the German Center for Neurodegenerative Diseases in Bonn.

University of Helsinki

Related Disease Articles:

Findings support role of vascular disease in development of Alzheimer's disease
Among adults who entered a study more than 25 years ago, an increasing number of midlife vascular risk factors, such as obesity, high blood pressure, diabetes, high cholesterol and smoking, were associated with elevated levels of brain amyloid (protein fragments linked to Alzheimer's disease) later in life, according to a study published by JAMA.
Dietary factors associated with substantial proportion of deaths from heart disease, stroke, and disease
Nearly half of all deaths due to heart disease, stroke, and type 2 diabetes in the US in 2012 were associated with suboptimal consumption of certain dietary factors, according to a study appearing in the March 7 issue of JAMA.
Study links changes in oral microbiome with metabolic disease/risk for dental disease
A team of scientists from The Forsyth Institute and the Dasman Diabetes Institute in Kuwait have found that metabolic diseases, which are characterized by high blood pressure, high blood sugar, and obesity -- leads to changes in oral bacteria and puts people with the disease at a greater risk for poor oral health.
Fatty liver disease contributes to cardiovascular disease and vice versa
For the first time, researchers have shown that a bi-directional relationship exists between fatty liver disease and cardiovascular disease.
Seroprevalence and disease burden of chagas disease in south Texas
A paper published in PLOS Neglected Diseases led by researchers at the National School of Tropical Medicine at Baylor College of Medicine suggests that the disease burden in southern Texas is much higher than previously thought.
More Disease News and Disease Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...