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

Two compounds in coffee may team up to fight Parkinson's

December 10, 2018
Rutgers scientists have found a compound in coffee that may team up with caffeine to fight Parkinson's disease and Lewy body dementia—two progressive and currently incurable diseases associated with brain degeneration.

New Parkinson's disease drug target revealed through study of fatty acids

December 4, 2018
The human brain is rich in lipids. Investigators studying Parkinson's disease (PD) have become increasingly interested in lipids since both molecular and genetic studies have pointed to the disruption of the balance of the ...

A toxin that travels from stomach to brain may trigger Parkinsonism

December 4, 2018
Combining low doses of a toxic herbicide with sugar-binding proteins called lectins may trigger Parkinsonism—symptoms typical of Parkinson's disease like body tremors and slowing of body motions—after the toxin travels ...

Experimental cancer drug shows promise for Parkinson's

December 3, 2018
The study, funded by Parkinson's UK, suggests that the drug, tasquinimod, which is not yet on the market, works by controlling genes that may cause Parkinson's. This happens when the drug interacts with a protein inside brain ...

Parkinson's therapy creates new brain circuits for motor function, study finds

November 28, 2018
Scientists have uncovered that an emerging gene therapy for Parkinson's disease creates new circuits in the brain associated with improved motor movement. These findings, published today in Science Translational Medicine ...

The puzzle of a mutated gene lurking behind many Parkinson's cases

November 15, 2018
Genetic mutations affecting a single gene play an outsized role in Parkinson's disease. The mutations are generally responsible for the mass die-off of a set of dopamine-secreting, or dopaminergic, nerve cells in the brain ...

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.