Researchers address sleep problems in Parkinson's disease

June 7, 2018, VIB (the Flanders Institute for Biotechnology)
Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

A team of researchers at VIB and KU Leuven has uncovered why people with a hereditary form of Parkinson's disease suffer from sleep disturbances. The molecular mechanisms uncovered in fruit flies and human stem cells also point to candidate targets for the development of new treatments.

Parkinson's affects 5 million people around the globe. Its typical symptoms are related to movement difficulty: tremor, rigidity, loss of balance. But patients are also faced with several non-motoric symptoms, including disturbed sleep. Nearly all patients experience some form of sleep pattern disturbance, ranging from nocturnal movements or insomnia to daytime sleepiness.

Problems with sleeping patterns are among the earliest symptoms of the disease, sometimes occurring as early as 10 years prior to the onset of motor symptoms and often before the actual diagnosis. Needless to say, this has a huge impact on people with Parkinson's and their loved ones.

Using induced human pluripotent derived from people with a hereditary form of Parkinson's disease, as well as genetically modified with Parkinson's symptoms, a team of scientists lead by Patrik Verstreken (VIB-KU Leuven Center for Brain & Disease Research) uncovered problems with the so-called neuropeptidergic , a specific type that regulates sleeping patterns.

Abnormal lipid trafficking in these neurons disrupts the production and release of neuropeptides, which in turn affects the regulation of sleep and circadian rhythms. The result is a disturbed sleep-wake cycle in the genetically modified flies.

"We uncovered which type of lipid is missing so we could try to rescue the sleep defects by restoring the lipid balance," explains Jorge Valadas, who is part of the Verstreken team. "When we model Parkinson's disease in fruit flies, we find that they have fragmented sleep patterns and difficulties in knowing when to go to sleep or when to wake up. But when we feed them phosphatidylserine—the lipid that is depleted in the neuropeptidergic neurons—we see an improvement in a matter of days."

The findings are promising, but the scientists underscore that a lot of work needs to be done before the results can be translated to patients.

Patrik Verstreken says, "Translating the phosphatidylserine experiments is not straightforward, as similar sleep manifestations are absent in mouse models of Parkinson's disease. The good news is that phosphatidylserine is already marketed as a food supplement, so if we can prove efficacy in humans, this would be very good news. There are still a lot of questions though. For example, we don't know if phosphatidylserine could be delivered to the brain in humans, or at which dose."

Non-motoric symptoms often receive less attention, but nonetheless have a major impact on patients' lives. Understanding and potentially intervening in what causes sleep problems in Parkinson's disease is thus an important step forward, but according to Verstreken, the findings are also a real conceptual game changer: "The main culprits of the motor symptoms are dopaminergic neurons, but the circadian rhythm and problems are specific to defects in neuropeptidergic neurons. Unlike for , the neuropeptidergic problems are caused by neuronal dysfunction, not degeneration, which implies that they can be corrected. This could be a real paradigm shift in the Parkinson's disease field."

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

More information: ER lipid defects in neuropeptidergic neurons impair sleep patterns in Parkinson's disease, Valadas et al., Neuron 2018.

Related Stories

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' ...

Promising cell study provides hope of effective treatment of Parkinson's disease

April 24, 2018
For the first time, medical doctors and researchers could alleviate serious symptoms of Parkinson's disease, which causes shaking, muscle stiffness and slow movements in those affected. However, before these symptoms appear, ...

Restless sleep may be an early sign of Parkinson's disease

December 6, 2017
Restless sleep could be a sign of a disorder associated with diseases of the brain. Researchers from Aarhus University conducted a case-control study on the condition of the dopamine-producing nerve cells in the brain and ...

New research suggests bowel cancer medication could help combat early-onset Parkinson's disease

March 14, 2017
People with certain forms of early-onset Parkinson's disease could potentially benefit from taking a medication used to treat certain forms of cancer, according to new research by University of Leicester scientists and funded ...

Finding the tipping point for sleep

January 5, 2018
Sleep is essential for many aspects of normal life, but how we actually fall asleep remains a mystery.

Recommended for you

New evidence sheds light on how Parkinson's disease may happen

June 14, 2018
Researchers at Baylor College of Medicine and Texas Children's Hospital have identified unexpected new key players in the development of an early onset form of Parkinson's disease called Parkinsonism. These key players are ...

Scientists unravel molecular mechanisms of Parkinson's disease

June 12, 2018
Detailed brain cell analysis has helped researchers uncover new mechanisms thought to underlie Parkinson's disease.

First photoactive drug to fight Parkinson's disease

June 8, 2018
An international team has designed the first potentially therapeutic photoactive drug, MRS7145, to fight Parkinson's disease, according to the new article in Journal of Controlled Release.

Researchers address sleep problems in Parkinson's disease

June 7, 2018
A team of researchers at VIB and KU Leuven has uncovered why people with a hereditary form of Parkinson's disease suffer from sleep disturbances. The molecular mechanisms uncovered in fruit flies and human stem cells also ...

Drugs that suppress immune system may protect against Parkinson's

May 31, 2018
People who take drugs that suppress the immune system are less likely to develop Parkinson's disease, according to a study from Washington University School of Medicine in St. Louis.

Early synaptic dysfunction found in Parkinson's Disease

May 24, 2018
Northwestern Medicine scientists identified a cellular mechanism that leads to neurodegeneration in patients with Parkinson's disease, according to a study published in Proceedings of the National Academy of Sciences.

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.