Mitochondrial lipids as potential targets in early onset Parkinson's disease

February 10, 2017

A team of researchers led by Patrik Verstreken (VIB–KU Leuven) have identified an underlying mechanism in early onset Parkinson's. Using flies, mice and patient cells, the team focused on cardiolipin, a fat unique to cells' mitochondria, organelles that produce energy. They demonstrated that reducing the effects of the protein FASN influences the mitochondria, leading to increased cardiolipin levels and reduced Parkinson's symptoms. These results could pave the way to therapies for Parkinson's disease that target lipids. The team's research was published in the scientific magazine Journal of Cell Biology.

An estimated 10 million people are currently affected by Parkinson's disease worldwide. A small percentage gets confronted with the disease before the age of 40. While the affection's causes are not yet known, scientists believe that they consist of both genetic and environmental factors. In genetic Parkinson's disease, a mutation in the PINK1 gene causes changes in neurons' , leading to the degeneration of these neurons.

Existing oncological applications

In this study, prof. Verstreken and his team, consisting of collaborators in Belgium, Germany and Portugal, observed that a protein responsible for lipid creation in cells, FASN, bypasses the genetic defect in mitochondria.

Prof. Patrik Verstreken (VIB–KU Leuven): "Several drugs that block FASN already exist, as this protein is also important to cancer research and treatment. Many of them have already been used in clinical trials. Thanks to this research, we can now test them in the context of Parkinson's disease."

Unexpected effects of FASN protein

In the course of their research, the researchers encountered a surprising observation. Using fly, mouse and human cell models, they saw that FASN has a direct effect on mitochondria, which have their own separate genomes and operate as energy producing entities within their cells.

Prof. Patrik Verstreken (VIB–KU Leuven): "The PINK1 gene encodes the PINK1 protein, and mutations in it lead to lower levels of cardiolipin in mitochondria. It was unexpected to see that blocking FASN – which is not localized to the mitochondria – actually sidesteps the mitochondrial effects of the PINK1 mutation. As a result, blocking FASN increases the amounts of a specific type of lipids in mitochondria, reducing the degradation of neurons."

Translating insights into therapies

Prof. Verstreken has already identified several targets for future research projects seeking greater insights into the link between the amounts of specific lipids in neurons and Parkinson's .

Prof. Patrik Verstreken (VIB–KU Leuven): "Some questions need to be answered before new therapies can be developed, such as 'is there a link between early onset Parkinson's prevalence and progression with lipid content?' And while we successfully demonstrated that cardiolipin can improve the function of mitochondria in flies, mouse models and in human cells, we need to explore its effects in actual patients."

Explore further: Vitamin K2: New hope for Parkinson's patients?

More information: Melissa Vos et al. Cardiolipin promotes electron transport between ubiquinone and complex I to rescuedeficiency, The Journal of Cell Biology (2017). DOI: 10.1083/jcb.201511044

Related Stories

Vitamin K2: New hope for Parkinson's patients?

May 11, 2012
Neuroscientist Patrik Verstreken, associated with VIB and KU Leuven, succeeded in undoing the effect of one of the genetic defects that leads to Parkinson's using vitamin K2. His discovery gives hope to Parkinson's patients. ...

Single mutation in recessive gene increases risk of earlier onset Parkinson's disease

November 2, 2016
A collaboration of 32 researchers in seven countries, led by scientists at Mayo Clinic's campus in Florida, has found a genetic mutation they say confers a risk for development of Parkinson's disease earlier than usual.

People with forms of early-onset Parkinson's disease may benefit from boosting niacin in diet, research suggests

January 10, 2017
University of Leicester research team leads new study strengthening therapeutic potential for dietary interventions.

Getting closer to treatment for Parkinson's

January 23, 2017
More than 10 million people worldwide have Parkinson's disease. The cause of Parkinson's disease is unknown and thus no effective treatments exist. A study from the University of Bergen (UiB) suggests that the secret of the ...

Faulty energy production in brain cells leads to disorders ranging from Parkinson's to intellectual disability

May 17, 2013
Neuroscientist Patrik Verstreken of VIB (Flanders Institute for Biotechnology) and KU Leuven has shown for the first time that dysfunctional mitochondria in brain cells can lead to learning disabilities. The link between ...

Scientists track down possible new treatment for epilepsy

September 26, 2016
Increasing the concentration of specific fats in the brain could suppress epileptic seizures. This is evident from ground-breaking research carried out by the research groups of Professor Patrik Verstreken (VIB-KU Leuven) ...

Recommended for you

Investigating the most common genetic contributor to Parkinson's disease

October 19, 2017
LRRK2 gene mutations are the most common genetic cause of Parkinson's disease (PD), but the normal physiological role of this gene in the brain remains unclear. In a paper published in Neuron, Brigham and Women's Hospital ...

Scientists solve 3-D structure of key defense protein against Parkinson's disease

October 5, 2017
Scientists at the University of Dundee have identified the structure of a key enzyme that protects the brain against Parkinson's disease.

Novel protein interactions explain memory deficits in Parkinson's disease

September 26, 2017
A study published in the journal Nature Neuroscience describes the identification of a novel molecular pathway that can constitute a therapeutic target for cognitive defects in Parkinson's disease. The study showed that abnormal ...

Psychosis in Parkinson's dementia—new treatment provides hope

September 25, 2017
New research involving King's College London and the University of Exeter has highlighted the benefits of a promising new treatment which could relieve psychosis in thousands of people with dementia related to Parkinson's ...

Bicycling 'overloads' movement networks with Parkinson's

September 23, 2017
(HealthDay)—Bicycling suppresses abnormal beta synchrony in the Parkinsonian basal ganglia, according to a study published online Sept. 11 in the Annals of Neurology.

Researchers find new path to promising Parkinson's treatment

September 19, 2017
Three researchers at The University of Alabama are part of work that is leading to a new direction for drug discovery in the quest to treat Parkinson's disease.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.