Researchers examining Parkinson's resilience

August 2, 2018 by Adam Jones, University of Alabama in Tuscaloosa
C. elegans, seen here as hundreds living on a plate viewed through the lens of a microscope, share roughly half their genes with humans. Credit: University of Alabama in Tuscaloosa

Diseases have a spectrum of risk, even those partially embedded in genes such as Parkinson's disease.

Less than 10 percent of those with Parkinson's can pinpoint their genes as the only culprit, while scores of others with some genetic markers are diagnosed with the disease. Still others have markers to develop Parkinson's, but do not.

Why? Research underway at The University of Alabama, supported by the National Institutes of Health, hopes to identify factors and methods through which individuals are either resilient or susceptible to the neurodegeneration in the brain as part of the disease.

"If we can pinpoint some of the factors that cause this distinction in resilience, then we can use them as a new therapeutic angle," said Dr. Guy Caldwell, University Distinguished Research Professor in biological sciences.

Caldwell, along with doctoral student Brucker Nourse, a native of Nashville, Tennessee, will work with tiny roundworms known as C. elegans, which share roughly half their genes with humans. Its basic features allow inexpensive and rapid testing for a range of neurological diseases, and UA researchers can induce Parkinson's-like effects in the worm for testing.

Even though the worms are essentially clones of each other from hermaphroditic reproduction, some animals develop Parkinson's-related effects while others do not, Caldwell said.

"We can learn from both the healthy and non-healthy," he said. "We hope we find genes that would potentially be part of a protective program."

Parkinson's disease, a neurodegenerative disorder, is estimated to afflict between 7 and 10 million people worldwide with approximately 60,000 Americans diagnosed each year. Current therapies include treating the symptoms of the disease such as tremor and involuntary shakes, but there is no cure or treatment to halt the disease's progression.

Hallmarks of Parkinson's disease are the loss of cells, or neurons, that send information to other parts of the brain, specifically neurons that produce a type of chemical known as dopamine, along with the accumulation, or clumping, of proteins in the neurons.

To work, proteins must fold properly within cells. When extra copies or mutations of the protein alpha-synuclein are present in dopamine-producing neurons, a series of misfoldings can occur, leading to aggregation of proteins. Such protein aggregation within the brain's can lead to their malfunction or cell death, triggering the symptoms of Parkinson's.

When a Parkinson's patient begins to exhibit symptoms of the disease, they have likely lost up to 80 percent of the dopamine neurons in their bodies, Caldwell said.

Since the worms all have an identical genetic code, Caldwell and Nourse are investigating how the genes of the worm are modified, or expressed. The turning off and on of genes from outside forces is known as epigenetics, and how external factors influence genetic performance is a big part of disease research, Caldwell said.

The research does not attempt to identify the external influences – after all, a worm has different stresses than a human – rather Caldwell hopes to determine which of the worm's genes, among those shared with humans, are associated with resilience to dopamine neuron loss.

"We're looking to bring together the unknown environmental causes and the known genetic causes in ways to potentially identify previously unknown protective factors and a previously unknown protective mechanism," Caldwell said.

Previous research published in the journal Science that Caldwell participated in uncovered a protein that regulated dopamine neuron survival. In fact, the research led to the discovery of a small molecule that protected neurons from dying. The molecule worked in several animal models and in human cells in the lab, but was later found not to cross what's known as the blood-brain barrier in humans, a sort of filter protecting the brain from unneeded materials.

In this newly funded research, Caldwell explores an exciting relationship he discovered whereby the same protective protein known to regulate dopamine function might also influence gene expression.

"That combination of regulating epigenetics and regulating dopamine levels and functions is the big mystery of Parkinson's. We really think this is a nexus of what might happen," Caldwell said. "There's promise there that if you can find a molecule to modulate that mechanism, and it crosses the , it might work at halting progression of the disease."

Explore further: Researchers find new path to promising Parkinson's treatment

Related Stories

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.

Researchers increase understanding of gene's potentially protective role in Parkinson's

February 7, 2012
Treatments for Parkinson's disease, estimated to affect 1 million Americans, have yet to prove effective in slowing the progression of the debilitating disease.

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.

Toward a better understanding of Parkinson's disease

July 4, 2018
A new study, published today in Nature Structural and Molecular Biology, moves researchers closer to understanding one of the crucial proteins involved in Parkinson's disease.

Team to study new gene associated with Parkinson's disease

June 15, 2018
A multidisciplinary team of researchers at Purdue University and the University of Bordeaux in France has received a grant from The Michael J. Fox Foundation for Parkinson's Disease to study a new gene associated with Parkinson's ...

Recommended for you

New transgenic model of Parkinson's illuminates disease biology

October 11, 2018
Parkinson's disease (PD) is a neurodegenerative disorder that presents clinically with abnormal movement and tremors at rest. In the brain, PD is marked by the accumulation of the protein, α-synuclein (αS), into clumps ...

Early Parkinson's patients waiting too long to seek medical evaluation

September 27, 2018
The time between diagnosis and the institution of symptomatic treatment is critical in the effort to find a cure for Parkinson's Disease (PD). A paper published in Nature Partner Journal: Parkinson's Disease notes too many ...

Molecule capable of halting and reverting neurodegeneration caused by Parkinson's disease identified

September 25, 2018
The small SynuClean-D molecule interrupts the formation of the alpha-synuclein amyloid fibres responsible for the onset of Parkinson's disease, and reverts the neurodegeneration caused by the disease. The study, headed by ...

Genomic dark matter activity connects Parkinson's and psychiatric diseases

September 20, 2018
Dopamine neurons are located in the midbrain, but their tendril-like axons can branch far into the higher cortical areas, influencing how we move and how we feel. New genetic evidence has revealed that these specialized cells ...

Gene therapy shown to remove core component of Parkinson's disease

September 14, 2018
An international team led by Rush researcher Jeffrey Kordower, Ph.D., has moved a step closer to developing a treatment to clear brain cells of a protein that is an integral cause of Parkinson's disease. The team published ...

ADHD may increase risk of Parkinson's disease and similar disorders

September 12, 2018
While about 11 percent of children (4-17 years old) nationwide have been diagnosed with attention-deficit hyperactivity disorder (ADHD), the long-term health effects of having ADHD and of common ADHD medications remains understudied. ...

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.