Discovery may point to Parkinson's disease therapies
University of Guelph researchers have discovered a key way Parkinson's disease spreads in the brain
2021-05-27
(Press-News.org) A new discovery by University of Guelph researchers may ultimately help in devising new therapies and improving quality of life for people with Parkinson's disease.
By showing how entangled proteins in brain cells enable the neurodegenerative disease to spread, the researchers hope their findings will lead to drugs that halt its progression, said PhD candidate Morgan Stykel, first author of a paper published this month in Cell Reports.
Parkinson's disease is the world's fastest-growing neurodegenerative disease and Canada has some of the world's highest rates, according to Parkinson Canada. Its exact cause is unknown.
Current therapies only treat symptoms rather than halting the disease, said Dr. Scott Ryan, a professor in the Department of Molecular and Cellular Biology who led the study.
Parkinson's disease can be triggered by the misfolding of a protein called alpha-synuclein that accumulates in a part of the brain called the substantia nigra. The disease causes loss of nerve cells in the brain that produce dopamine, a chemical messenger that helps control motor function.
Misfolded alpha-synuclein aggregates and eventually spreads to other parts of the brain, impairing areas responsible for other functions such as mood and cognition.
The U of G team used stem cells to model neurons with and without Parkinson's disease and look at the effects of synuclein mutations.
They discovered that in Parkinson's neurons, misfolded synuclein binds to another protein called LC3B. Normally, LC3B targets misfolded proteins to be degraded. In Parkinson's disease, the study showed, LC3 gets trapped in the protein aggregates and is inactivated.
Without degradation, the cells eject the aggregates, which then spread to nearby neurons, propagating the disease throughout the brain.
"Normally misfolded proteins are degraded. We found a pathway by which synuclein is being secreted and released from neurons instead of being degraded," said Ryan. "We hope to turn the degradation pathway back on and stop the spread of disease."
The team showed that activating LC3B restores degradation, enabling cells to clear the misfolded proteins and prevent disease spread.
"Regular protein turnover is part of a healthy cell," said Stykel. "With Parkinson's disease, that system is not working properly."
Ryan said their finding could help in devising therapies.
"We may not be able to do anything about brain regions that are already diseased, but maybe we can stop it from progressing. We might be able to turn the degradation pathway back on and stop the spread of the disease."
He cautioned that other biochemical pathways are also likely involved in the spread of the disease through the brain. Still, the finding provides a target for potential drug development.
"Most current therapies centre around increasing the release of dopamine, but that works for a brief period and has a lot of side effects," said Ryan.
This research may help improve quality of life for Parkinson's patients. Many patients are diagnosed in their 40s or 50s, meaning that they live with the progressive disease for decades.
"Reduced quality of life can be a huge burden on patients, their families and the health-care system," he said.
INFORMATION:
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
2021-05-27
In the largest genetic analysis of depression to date, Veterans Affairs researchers identified many new gene variants that increase the risk for depression. The groundbreaking study helps researchers better understand the biological basis of depression and could lead to better drug treatments.
The study involved genetic data on more than 300,000 participants of VA's Million Veteran Program (MVP), along with more than a million subjects from other biobanks, including 23andMe. With such a large participant pool, the researchers were able to spot trends in genetic risk of depression not previously known.
Co-primary investigator Dr. Joel Gelernter, a researcher with the VA Connecticut Healthcare System and Yale University School of Medicine, explained ...
2021-05-27
Researchers at the University of Illinois Chicago are a step closer to discovering why it is so difficult for people to withdraw from some antidepressant medications.
The paper "Antidepressants produce persistent Gαs associated signaling changes in lipid rafts following drug withdrawal," published in the journal Molecular Pharmacology, addresses the molecular and cellular mechanisms that cause antidepressant withdrawal syndrome.
The study's authors, Mark Rasenick, distinguished professor of physiology and biophysics and psychiatry at UIC and research career scientist at the Jesse Brown VA Medical Center, and Nicholas ...
2021-05-27
Higher percentage of patients treated with nivolumab and ipilimumab in clinical trial reach the six-and-a-half-year survival mark than those treated with either drug alone.
BOSTON - In the longest follow-up results from a clinical trial of combination immunotherapy for metastatic melanoma, investigators report that nearly half the patients who received the drugs nivolumab and ipilimumab were alive a median of six and a half years after treatment. The results, stemming from the CheckMate 067 clinical trial, represent a new landmark in survival rates for patients with melanoma treated with immune checkpoint inhibitor drugs.
F. ...
2021-05-27
URBANA, Ill. - As the owner of a human body, you're carrying trillions of microbes with you everywhere you go. These microscopic organisms aren't just hitching a ride; many of them perform essential chemical reactions that regulate everything from our digestion to our immune system to our moods.
One important set of reactions relates to fat absorption via bile acids. Our livers make these acids to help digest fats and fat-soluble vitamins as they travel through the small intestine. Near the end of the small intestine, microbes convert the acids into new forms, which can either be beneficial or ...
2021-05-27
Over the past 20 years, first-principles simulations have become powerful, widely used tools in many, diverse fields of science and engineering. From nanotechnology to planetary science, from metallurgy to quantum materials, they have accelerated the identification, characterization, and optimization of materials enormously. They have led to astonishing predictions--from ultrafast thermal transport to electron-phonon mediated superconductivity in hydrides to the emergence of flat bands in twisted-bilayer graphene-- that have gone on to inspire remarkable experiments.
The current push to complement ...
2021-05-27
WASHINGTON -- Researchers have developed a new technique that allows microscopic fluorescence imaging at four times the depth limit imposed by light diffusion. Fluorescence microscopy is often used to image molecular and cellular details of the brain in animal models of various diseases but, until now, has been limited to small volumes and highly invasive procedures due to intense light scattering by the skin and skull.
"Visualization of biological dynamics in an unperturbed environment, deep in a living organism, is essential for understanding the complex biology of living organisms ...
2021-05-27
Five years on from the first discovery of gravitational waves, an international team of scientists, including from the ARC Centre of Excellence for Gravitational Wave Discovery (OzGrav), are continuing the hunt for new discoveries and insights into the Universe. Using the super-sensitive, kilometre-sized LIGO detectors in the United States, and the Virgo detector in Europe, the team have witnessed the explosive collisions of black holes and neutron stars. Recent studies, however, have been looking for something quite different: the elusive signal from a solitary, rapidly-spinning neutron star.
Take a star similar in size to the Sun, squash it down to a ball about ...
2021-05-27
The hunt for the never before heard "hum" of gravitational waves caused by mysterious neutron stars has just got a lot easier, thanks to an international team of researchers.
Gravitational waves have only been detected from black holes and neutron stars colliding, major cosmic events that cause huge bursts that ripple through space and time.
The research team, involving scientists from the LIGO Scientific Collaboration (LSC), Virgo Collaboration and the Centre for Gravitational Astrophysics (CGA) at The Australian National University (ANU), are now turning their eagle eye to spinning neutron stars to detect the waves.
Unlike the massive bursts caused by black holes or neutron stars colliding, the researchers ...
2021-05-27
AMHERST, Mass. - New research by University of Massachusetts Amherst astronomer Daniel Wang reveals, with unprecedented clarity, details of violent phenomena in the center of our galaxy. The images, published recently in Monthly Notices of the Royal Astronomical Society, document an X-ray thread, G0.17-0.41, which hints at a previously unknown interstellar mechanism that may govern the energy flow and potentially the evolution of the Milky Way.
"The galaxy is like an ecosystem," says Wang, a professor in UMass Amherst's astronomy department, whose findings are a result of more than two decades of research. "We know the centers of galaxies are where the action is and play an enormous role in their evolution." And yet, whatever has ...
2021-05-27
Individuals with genetic high cholesterol, heart disease or both, who were infected with COVID-19 had more heart attacks according to new research by the FH Foundation. While previous studies have speculated about poorer outcomes if a person with genetic high cholesterol - called familial hypercholesterolemia (FH) contracts COVID-19, this study from the FH Foundation's national healthcare database is the first to demonstrate higher heart attack rates in the real world. Published online in the American Journal of Preventive Cardiology, the study also importantly confirms that COVID-19 increases heart attack rates in individuals with established atherosclerotic cardiovascular disease (ASCVD).
The FH Foundation performed an analysis of 55,412,462 individuals, separating groups into six ...
LAST 30 PRESS RELEASES:
[Press-News.org] Discovery may point to Parkinson's disease therapies
University of Guelph researchers have discovered a key way Parkinson's disease spreads in the brain
