(Press-News.org) Researchers at the University of Toronto have found a way to better control the preclinical generation of key neurons depleted in Parkinson’s disease, pointing toward a new approach for a disease with no cure and few effective treatments.
The researchers used an antibody to selectively activate a receptor in a molecular signaling pathway to develop dopaminergic neurons. These neurons produce dopamine, a neurotransmitter critical to brain health.
Researchers around the world have been working to coax stem cells to differentiate into dopaminergic neurons, to replace those lost in patients living with Parkinson’s disease. But efforts have been hindered in part by an inability to target specific receptors and areas of the brain.
“We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway,” said Stephane Angers, principal investigator on the study and director of the Donnelly Centre for Cellular and Molecular Biology.
“We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway,” said Angers, who is also a professor in the Leslie Dan Faculty of Pharmacy and the Temerty Faculty of Medicine, and holds the Charles H. Best Chair of Medical Research at U of T. “This activation method has not been explored before.”
The study was recently published in the journal Development.
Parkinson’s disease is the second-most common neurological disorder after Alzheimer’s, affecting over 100,000 Canadians. It particularly impacts older men, progressively impairing movement and causing pain as well as sleep and mental health issues.
Most previous research efforts to activate the Wnt signaling pathway have relied on a GSK3 enzyme inhibitor. This method involves multiple signaling pathways for stem cell proliferation and differentiation, which can lead to unintended effects on the newly produced neurons and activation of off-target cells.
“We developed an efficient method for stimulating stem cell differentiation to produce neural cells in the midbrain,” said Andy Yang, first author on the study and a PhD student at the Donnelly Centre. “Moreover, cells activated via the FZD5 receptor closely resemble dopaminergic neurons of natural origin.”
Another promising finding of the study was that implanting the artificially-produced neurons in a rodent model with Parkinson’s disease led to improvement of the rodent’s locomotive impairment.
“Our next step would be to continue using rodent or other suitable models to compare the outcomes of activating the FZD5 receptor and inhibiting GSK3,” said Yang. “These experiments will confirm which method is more effective in improving symptoms of Parkinson’s disease ahead of clinical trials.”
This research was supported by the University of Toronto Medicine by Design program, which receives funding from the Canada First Research Excellence Fund, and the Canadian Institutes of Health Research.
END
U of T researchers target neurogenesis in new approach to treat Parkinson’s disease
2024-04-30
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
Microbiome researchers challenge the state of the art in colon cancer biomarker discovery
2024-04-30
Leuven (Belgium) 30/04/2024 - For the first time, researchers from VIB-KU Leuven, UZ Leuven, Janssen Pharmaceutica and multiple international collaborators have introduced quantitative methods and extensive confounder control to discover microbiome biomarkers in colorectal cancer development. While multiple microbial taxa have been put forward as potential cancer-associated biomarkers in the past, this new study uncovers obscured contributions that may have resulted in incorrect associations. The results have been published in Nature Medicine.
Cancer ...
Unveiling nature's custodians: groundbreaking study highlights crucial role of scavengers in wetlands
2024-04-30
A pioneering study highlights the importance of carrion and scavengers in wetlands on a global scale. A study by researchers from the Ecology area of the Miguel Hernández University of Elche (UMH) and the Ecology department of the University of Alicante (UA) reveals the fundamental importance of scavengers and carrion in wetlands. The article, published in Biological Reviews, emphasizes that the benefits provided by scavengers far outweigh the potential drawbacks. Among their essential functions are the recycling and transportation of nutrients and the regulation of water quality, benefiting the entire ecosystem, from soil and plants to birds and mammals.
Historically, ...
Data scarcity challenges identification of endocrine disruptors
2024-04-30
As a result, the researchers recommend updating the information requirements in the EU legislation, REACH. They also propose various approaches for evaluating chemical substances to ensure that all available information is fully utilized.
Researchers from DTU National Food Institute and the University of Southern Denmark have screened the scientific literature for the Danish Environmental Protection Agency to find substances showing signs of endocrine disrupting properties and thus being potentially harmful to humans and ...
A significant portion of the world’s population continues to trust vaccines, says survey in 23 countries
2024-04-30
A substantial proportion of the world’s population remains willing to get vaccinated against diseases including COVID-19, according to a new survey across 23 countries that represent more than 60% of the world’s population. The study, published in Nature Medicine, was co-led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa” Foundation, and the Graduate School of Public Health and Health Policy of the City University of New York (CUNY SPH).
The severe human impact of the COVID-19 pandemic led to the rapid research and development of safe and effective vaccines based on existing models, ...
Clumps of this molecule inhibit strep’s DNA-cleaving enzymes
2024-04-30
An entirely new approach to inhibiting DNA-cleaving enzymes works through the aggregation of an otherwise non-toxic molecule. This Kobe University discovery may lead to a much-needed method for curbing Streptococcus growth.
Enzymes are the body’s tools to make almost all reactions happen. But the same is true for bacteria like Streptococcus, which causes toxic shock syndrome, a rapidly progressing and deadly condition. When the body’s white blood cells try to capture the bacteria by casting nets made out ...
Cars as particles
2024-04-30
What do the flow of cars on a highway and the movement of bacteria towards a food source have in common? In both cases, annoying traffic jams can form. Especially for cars, we might want to understand how to avoid them, but perhaps we've never thought of turning to statistical physics, as Alexandre Solon, a physicist from Sorbonne Université, and Eric Bertin, from the University of Grenoble, both working for the Centre national de la recherche scientifique CNRS, have done. Their research, recently published in the Journal of Statistical Mechanics: Theory and Experiment (JSTAT), has developed a one-dimensional mathematical model ...
Let widgeongrass be a weed in the seagrass yard -- making seagrass restoration more resistant to rising temperatures using generalist grasses
2024-04-30
New research demonstrates that seagrass habitat restoration can be enhanced by including other grasses in addition to the declining or lost species and – ultimately – that restoration efforts must proactively select species that can withstand current and intensifying stressors driven by human activities and climate change.
Rising global temperatures combined with centuries of humans working within our seascapes has reshaped coastal ecosystems. Rebuilding or restoring coastal habitat is becoming ...
Group sales incentives boost weak brand sales, study finds
2024-04-30
New research co-authored by a UC Riverside business professor provides some sound advice for managers of retail outlets that limit their product selection to a particular brand: Managers should factor in the strength of their brand when structuring the pay incentives for their sales staff.
The study focused on what marketing scholars call “brand-managed” retail operations. These outlets include “stores within stores,” such as counters in major department stores with dedicated sales staff that offer just one brand of cosmetics such as Clinique. They can also be stores ...
The double-fanged adolescence of saber-toothed cats
2024-04-30
The fearsome, saber-like teeth of Smilodon fatalis — California's state fossil — are familiar to anyone who has ever visited Los Angeles' La Brea Tar Pits, a sticky trap from which more than 2,000 saber-toothed cat skulls have been excavated over more than a century.
Though few of the recovered skulls had sabers attached, a handful exhibited a peculiar feature: the tooth socket for the saber was occupied by two teeth, with the permanent tooth slotted into a groove in the baby tooth.
Paleontologist Jack Tseng, associate professor of integrative biology at the University of California, Berkeley, doesn't think the double fangs ...
COVID-19-induced financial hardships reveal mental health struggles
2024-04-30
When COVID-19 caused significant economic disruptions, thousands of people around the world experienced sudden shocks to their financial situation through reduced earnings or job losses.
Now economic researchers at the University of South Australia have examined the mental health effects on people who experienced immediate or expected financial setbacks during the height of the pandemic.
Data gathered from China, Japan and South Korea during the early phases of the pandemic revealed that the severe economic shocks induced by COVID-19 caused significant ...