Study uncovers cause of cell death in Parkinson's disease

February 26, 2018, University of Guelph
Credit: CC0 Public Domain

A University of Guelph researcher has discovered one of the factors behind nerve cell death in Parkinson's disease, unlocking the potential for treatment to slow the progression of this fatal neurodegenerative disorder.

Prof. Scott Ryan has found that cardiolipin, a molecule inside , helps ensure that a called alpha-synuclein folds properly. Misfolding of this protein leads to protein deposits that are the hallmark of Parkinson's disease.

These deposits are toxic to nerve that control voluntary movement. When too many of these deposits accumulate, nerve cells die.

"Identifying the crucial role cardiolipin plays in keeping these proteins functional means cardiolipin may represent a new target for development of therapies against Parkinson's disease," said Ryan, a professor in U of G's Department of Molecular and Cellular Biology. "Currently there are no treatments that stop nerve cells from dying."

Parkinson's disease is the most common degenerative movement disorder in Canada, affecting about 100,000 people.

Published in the journal Nature Communications, the study used stem cells collected from people with the disease. Ryan's research team studied how nerve cells try to cope with misfolded alpha-synuclein.

"We thought if we can better understand how cells normally fold alpha-synuclein, we may be able to exploit that process to dissolve these aggregates and slow the spread of the disease," he said.

Funded by Parkinson Canada, the study revealed that, inside cells, alpha-synuclein binds to mitochondria, where cardiolipin resides. Cells use mitochondria to generate energy and drive metabolism.

Normally, cardiolipin in mitochondria pulls synuclein out of toxic protein deposits and refolds it into a non-toxic shape.

The U of G researchers found that, in people with Parkinson's disease, this process is overwhelmed over time and mitochondria are ultimately destroyed, said Ryan.

"As a result, the cells slowly die. Based on this finding, we now have a better understanding of why nerve cells die in Parkinson's disease and how we might be able to intervene."

He said understanding cardiolipin's role in protein refolding may help in creating a drug or therapy to slow progression of the disease.

"The hope is that we will be able to rescue locomotor deficits in an animal model. It's a big step towards treating the cause of this disease."

Explore further: Calcium may play a role in the development of Parkinson's disease

More information: Tammy Ryan et al, Cardiolipin exposure on the outer mitochondrial membrane modulates α-synuclein, Nature Communications (2018). DOI: 10.1038/s41467-018-03241-9

Related Stories

Calcium may play a role in the development of Parkinson's disease

February 19, 2018
Researchers have found that excess levels of calcium in brain cells may lead to the formation of toxic clusters that are the hallmark of Parkinson's disease.

Shedding a tear may help diagnose Parkinson's disease

February 22, 2018
Tears may hold clues to whether someone has Parkinson's disease, according to a preliminary study released today that will be presented at the American Academy of Neurology's 70th Annual Meeting in Los Angeles, April 21 to ...

Molecular link between Parkinson's disease and prion diseases

September 15, 2017
Parkinson's disease and prion diseases are very different as regards both origins and course. Nonetheless, a research group of SISSA, headed by Professor Giuseppe Legname, has discovered an unexpected and important link between ...

Drug discovery: Alzheimer's and Parkinson's spurred by same enzyme

July 3, 2017
Alzheimer's disease and Parkinson's disease are not the same. They affect different regions of the brain and have distinct genetic and environmental risk factors.

Pre-clinical study suggests Parkinson's could start in gut endocrine cells

June 15, 2017
Recent research on Parkinson's disease has focused on the gut-brain connection, examining patients' gut bacteria, and even how severing the vagus nerve connecting the stomach and brain might protect some people from the debilitating ...

A new insight into Parkinson's disease protein

July 28, 2017
Abnormal clumps of certain proteins in the brain are a prominent feature of Parkinson's and other neurodegenerative diseases, but the role those same proteins might play in the normal brain has been unknown.

Recommended for you

The eyes may have it, an early sign of Parkinson's disease

August 16, 2018
The eyes may be a window to the brain for people with early Parkinson's disease. People with the disease gradually lose brain cells that produce dopamine, a substance that helps control movement. Now a new study has found ...

First-of-its-kind Parkinson's biomarker guidelines invigorates drive for treatments

August 15, 2018
Parkinson's disease affects more than 4 million people worldwide, with numbers projected to double in the next few decades. With no known cure, there is a race for treatments to slow or stop the progression of the disease. ...

Study identifies chaperone protein implicated in Parkinson's disease

August 13, 2018
Reduced levels of a chaperone protein might have implications for the development and progression of neurodegenerative diseases such as Parkinson's disease and Lewy body dementia, according to new research from investigators ...

Function of gene mutations linked to neurological diseases identified

August 10, 2018
Several gene mutations have been linked to Parkinson's disease, but exactly how and where some of them cause their damage has been unclear. A new Yale study, published in the Journal of Cell Biology, shows that one of the ...

Biomarkers link fatigue in cancer, Parkinson's

August 9, 2018
Biological markers responsible for extreme exhaustion in patients with cancer have now been linked to fatigue in those with Parkinson's disease, according to new research from Rice University.

Researchers examining Parkinson's resilience

August 2, 2018
Diseases have a spectrum of risk, even those partially embedded in genes such as 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.