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

High-intensity exercise delays Parkinson's progression

December 11, 2017
High-intensity exercise three times a week is safe for individuals with early-stage Parkinson's disease and decreases worsening of motor symptoms, according to a new phase 2, multi-site trial led by Northwestern Medicine ...

Changes in diet may improve life expectancy in Parkinson's patients

November 24, 2017
New research from the University of Aberdeen shows that weight loss in people with Parkinson's disease leads to decreased life expectancy, increased risk of dementia and more dependency on care.

Good cells gone bad: Scientists discover PINK-SNO

November 21, 2017
A new study from The Scripps Research Institute (TSRI) is the first to show precisely how a process in nerve cells called the S-nitrosylation (SNO) reaction—which can be caused by aging, pesticides and pollution—may contribute ...

Genetic defects in the cell's 'waste disposal system' linked to Parkinson's disease

November 14, 2017
An international study has shed new light on the genetic factors associated with Parkinson's disease, pointing at a group of lysosomal storage disorder genes as potential major contributors to the onset and progression of ...

Parkinson's disease: A looming pandemic

November 13, 2017
New research shows that the number of people with Parkinson's disease will soon grow to pandemic proportions. In a commentary appearing today in the journal JAMA Neurology, University of Rochester Medical Center neurologist ...

Focused ultrasound shows promise for treating Parkinson's tremor

October 30, 2017
An initial test to determine if a scalpel-free form of brain surgery can reduce tremor caused by Parkinson's disease has produced encouraging results. Further research is warranted, the researchers conclude in a paper published ...

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.