Alzheimer's-disease-related proteases control axonal guidance by regulating growth cone dynamics
(Press-News.org) Alzheimer's-disease-related proteases, BACE1 and APH1B-y-secretase, control axonal guidance by regulating growth cone dynamics
BACE1 is the major drug target for Alzheimer's disease, but we know surprisingly little about its normal function in the CNS. Soraia Barão and Bart De Strooper (VIB/KU Leuven) now show that this protease is critically involved in axonal guidance processes in thalamic and hippocampal neurons. An active membrane bound proteolytic CHL1 fragment is generated by BACE1 upon Sema3A binding. This fragment relays the Sema3A signal to the neuronal cytoskeleton. APH1B-y-secretase- mediated degradation of this fragment stops the Sema3A-induced collapse and sensitizes the growth cone for the next axonal guidance cue.
Soraia Barão (VIB/KU Leuven): "We reveal a cycle of proteolytic activity underlying growth cone collapse and restoration used by axons to find their correct trajectory in the brain. Our data show that BACE1 and y-secretase inhibition have physiologically opposite effects in this process, suggesting that cautiously-designed combination therapies might attenuate some of the side effects associated with these drugs."
Bart De Strooper (VIB/KU Leuven): "Based on this new knowledge of the functions of both proteases (BACE1 cleaves CHL1, inducing growth cone collapse. Subsequently, y-secretase activity stops the collapse and axonal growth resumes.), we think it wise to proceed the testing of inhibitors of these proteases in humans with caution."
Antagonistic Effects of BACE1 and APH1B-y-Secretase Control Axonal Guidance by Regulating Growth Cone Collapse, Barão et al., Cell Reports 2015
ELSE PRESS RELEASES FROM THIS DATE:
Persons sleeping less than 6 hours or more than 10 hours suffer from low-grade inflammation more often than persons sleeping 7-8 hours per night. This was observed in a University of Eastern Finland study focusing on the health and lifestyle habits among middle-aged men.
"Earlier studies have found a relation between reduced sleep and low-grade inflammation," says Maria Luojus, MHSc, one of the study researchers.
Furthermore, low-grade inflammation occurs in overweight, depression and diabetes.
The study is the first to analyse the association between sleep duration ...
Results of a 20-year follow-up of the academic EORTC 22881-10882 boost no-boost trial presented as a "Best Abstract" at the European Cancer Congress 2015 in Vienna show that young age, high-grade invasive tumor, and the presence of associated ductal carcinoma in situ were all factors increasing the local recurrence rate. An earlier analysis had already shown that young age and high-grade invasive carcinoma were the most important risk factors for local relapse in this trial conducted from 1989 to 1996.
Dr. Conny Vrieling of the Clinique des Grangettes in Geneva, Switzerland, ...
A new study has confirmed that regular smokers have a significantly increased risk of tooth loss.
Male smokers are up to 3.6 times more likely to lose their teeth than non-smokers, whereas female smokers were found to be 2.5 times more likely.
The research, published in the Journal of Dental Research, is the output of a long-term longitudinal study of the EPIC Potsdam cohort in Germany carried out by researchers at the University of Birmingham and the German Institute of Human Nutrition.
Tooth loss remains a major public health problem worldwide. In the UK, 15% of ...
Malnutrition is a known complication of weight loss surgery, but findings from a small study by researchers at Johns Hopkins show many obese people may be malnourished before they undergo the procedure.
"Our results highlight the often-overlooked paradox that abundance of food and good nutrition are not one and the same," says senior investigator Kimberley Steele, M.D., Ph.D., associate professor of surgery at the Johns Hopkins University School of Medicine. "Overweight and obese people can suffer from nutritional deficiencies, and those who care for them should be aware ...
Telecommunication networks will soon reach the physical limits of current technology and in order to overcome the current bottleneck, they will have to exploit the quantum properties of light. Roberto Morandotti and his INRS team are paving the way to this technological revolution by removing the technical barriers of quantum photonics through the use of their optical chips. Recently they directly generated cross-polarized (orthogonal) photon pairs on a chip, a first in quantum optics. Polarization will now be among the controllable parameters for harnessing light in a ...
The first images of motor proteins in action are published in the journal Nature Communications today.
These proteins are vital to complex life, forming the transport infrastructure that allows different parts of cells to specialise in particular functions. Until now, the way they move has never been directly observed.
Researchers at the University of Leeds and in Japan used electron microscopes to capture images of the largest type of motor protein, called dynein, during the act of stepping along its molecular track.
Dr Stan Burgess, at the University of Leeds' ...
Elephants born into stressful situations have fewer offspring and age faster, researchers at the University of Sheffield have found.
Scientists discovered that Asian elephants born during times when their mothers experience highest stress levels produce significantly fewer offspring in their lifetime despite having higher rates of reproduction at an early age.
The research team, from the University's Department of Animal and Plant Sciences, also found that those animals born under stress declined much more rapidly in older age, decades later.
Lead author Dr Hannah ...
Eating a Mediterranean diet supplemented with extra virgin olive oil was associated with a relatively lower risk of breast cancer in a study of women in Spain, according to an article published online by JAMA Internal Medicine.
Breast cancer is a frequently diagnosed cancer and a leading cause of death in women. Diet has been extensively studied as a modifiable risk factor in the development of breast cancer but epidemiologic evidence on the effect of specific dietary factors is inconsistent.
The Mediterranean diet is known for its abundance of plant foods, fish and ...
A new study reveals that insurance status, marital status, and county-level income may affect the chances of survival in young patients with acute myelogenous leukemia (AML). Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings indicate that efforts are needed to address the social factors that impact critical aspects of health in these patients.
AML will affect approximately 20,830 and kill 10,460 Americans in 2015. Tremendous progress has been made in identifying disease characteristics that cause a patient to have ...
A new protocol to treat babies born in withdrawal from drugs can be used widely to improve outcomes for these babies.
The protocol reduces length of stay and the duration of treatment with opioids that are used therapeutically to wean babies off of drugs.
"The incidence of neonatal abstinence syndrome after an infant's in utero exposure to opioids has risen dramatically in recent years," says Eric Hall, PhD, a researcher in the Perinatal Institute at Cincinnati Children's and lead author of the study. "After adoption of the protocol, opioid treatment went from 34 to ...
LAST 30 PRESS RELEASES: