(Press-News.org) https://doi.org/10.1016/j.apsb.2024.02.004
This new article publication from Acta Pharmaceutica Sinica B, discusses how ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction.
Growing evidence indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative disorders. The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72 (C9orf72) is the most genetic cause of both ALS and FTD.
According to previous studies, GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation, which produces dipeptide repeat (DPR) proteins. Although there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD, whether these DPRs can affect autophagy remains unclear.
In this article the authors report that poly-GR and poly-PR, two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies, strongly inhibit starvation-induced autophagy. Moreover, the data indicates that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation, therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in cells.
This study not only highlights the role of C9orf72 DPR in autophagy dysfunction, but also provides novel insight that pharmacological intervention of autophagy using SW063058, a small molecule compound that can disrupt the interaction between BECN1 and BCL2, may reduce C9orf72 DPR-induced neurotoxicity.
Keywords: Amyotrophic lateral sclerosis, Frontotemporal dementia, C9orf72, Autophagy, BCL2, BECN1/Beclin 1, Dipeptide repeat, Neurodegeneration
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S221138352400042X-ga1.jpg
ALS/FTD-linked C9orf72 DPRs inhibit starvation-induced autophagy by enhancing BCL2–BECN1/Beclin 1 interaction. Under this condition, pharmacological disruption of the interaction between BECN1 and BCL2 can restore autophagy and may therefore reduce C9orf72 DPR-induced neurotoxicity.
# # # # # #
The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.
For more information please visit https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/
Editorial Board: https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/editorial-board
APSB is available on ScienceDirect (https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b).
Submissions to APSB may be made using Editorial Manager® (https://www.editorialmanager.com/apsb/default.aspx).
CiteScore: 19.4
Impact Factor: 14.5
JIF without self-citation: 13.7
ISSN 2211-3835
# # # # #
Shiqiang Xu, Qilian Ma, Junwen Shen, Ningning Li, Shan Sun, Nana Wang, Yang Chen, Chunsheng Dong, Kin Yip Tam, Jochen H.M. Prehn, Hongfeng Wang, Zheng Ying, ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction, Acta Pharmaceutica Sinica B, Volume 14, Issue 5, 2024, Pages 2026-2038, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2024.02.004
END
Researchers at the Department of Energy’s Oak Ridge National Laboratory are developing battery technologies to fight climate change in two ways, by expanding the use of renewable energy and capturing airborne carbon dioxide.
This type of battery stores the renewable energy generated by solar panels or wind turbines. Utilizing this energy when wind and sunlight are unavailable requires an electrochemical reaction that, in ORNL’s new battery formulation, captures carbon dioxide from industrial emissions and converts it to value-added products.
ORNL researchers recently created and tested two different formulations for batteries that ...
Georgia’s saltwater marshes — living where the land meets the ocean — stretch along the state’s entire 100-mile coastline. These rich ecosystems are largely dominated by just one plant: grass.
Known as cordgrass, the plant is an ecosystem engineer, providing habitats for wildlife, naturally cleaning water as it moves from inland to the sea, and holding the shoreline together so it doesn’t collapse. Cordgrass even protects human communities from tidal surges.
Understanding how these ...
The onset of the COVID-19 pandemic changed how nearly everyone mediated their social interactions through technology. Some moved happy hours into video chats. Others delved deeper into social media, or took a step back from it. Millions of people worked or learned through computers.
University of Washington researchers took particular interest in how this tech shift affected older adults’ social relationships. The team interviewed 16 older adults in Washington and Oregon, ages 65 to 80, about how their technology ...
Records from nearly 30,000 nursing home residents indicate that blood pressure medications more than double the risk of life-threatening bone fractures, according to Rutgers Health research.
The authors of the study, which appears in JAMA Internal Medicine, said the increased risk stems from the medications’ tendency to impair balance, particularly when patients first stand up and temporarily experience low blood pressure that deprives the brain of oxygen. Interactions with other drugs and low baseline balance in many nursing home patients compound the problem.
“Bone fractures often start nursing home patients on a downward spiral,” ...
Many organisms are far more complex than just a single species. Humans, for example, are full of a variety of microbes. Some creatures have even more special connections, though. Acoels, unique marine worms that regenerate their bodies after injury, can form symbiotic relationships with photosynthetic algae that live inside them. These collections of symbiotic organisms are called a holobiont, and the ways that they “talk” to each other are something scientists are trying to understand – especially ...
Compared with pre-surgical (neoadjuvant) chemotherapy alone, adding perioperative immunotherapy – given before and after surgery – significantly improved event-free survival (EFS) in patients with resectable early-stage non-small cell lung cancer(NSCLC), according to researchers from The University of Texas MD Anderson Cancer Center.
Results from the Phase III CheckMate 77T study were published today in the New England Journal of Medicine. At a median follow-up of 25.4 months, the median EFS with chemotherapy alone was 18.4 months, while the median had not yet ...
“I consider the drugs available on the marked today as the first generation of weight-loss drugs. Now we have developed a new type of weight-loss drug that affects the plasticity of the brain and appears to be highly effective.”
So says Associate Professor and Group Leader Christoffer Clemmensen, from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, who is senior author of the new study, which has been published in the prestigious scientific journal Nature.
In the study, Christoffer Clemmensen and colleagues demonstrate a new use of the weight loss hormone GLP-1. GLP-1 can be used as a ‘Trojan ...
Bariatric surgery is associated with a reduced risk of breast cancer in women with obesity. These are the findings of a study conducted at the University of Gothenburg. The risk reduction is greatest for those with high blood insulin levels at the time of surgery.
The study, published in JAMA Surgery, is based on data from 2,867 women with obesity, half of whom had undergone bariatric surgery at 25 surgical departments. The remaining women, comprising the control group, received standard obesity treatment at 480 healthcare centers. The groups were otherwise comparable in terms of age and body composition.
The results show that a total of ...
Copper cannot be mined quickly enough to keep up with current U.S. policy guidelines to transition the country's electricity and vehicle infrastructure to renewable energy, according to a University of Michigan study.
The Inflation Reduction Act, signed into law in 2022, calls for 100% of cars manufactured to be electric vehicles by 2035. But an electric vehicle requires three to five times as much copper as an internal combustion engine vehicle—not to mention the copper required for upgrades to the electric grid.
"A ...
EMBARGOED FOR RELEASE UNTIL 4 P.M. ET, WEDNESDAY, MAY 15, 2024
MINNEAPOLIS – A new guideline has been issued to help neurologists and other clinicians determine the best antiseizure medications for people with epilepsy who may become pregnant. The guideline is published in the May 15, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology (AAN), and was developed through a collaboration between the AAN, the American Epilepsy Society (AES) and the Society for Maternal-Fetal Medicine (SMFM). It was endorsed by the Child Neurology Society.
The guideline partially updates two 2009 AAN and AES ...
