Summary: Lemborexant, a common sleep aid, may do more than just market rest; it appears to reduce dangerous beta buildup and guard the brain from degeneration in mouse models of Alzheimer’s disease. This orexin sensor enemy, according to experts, not only improved sleep patterns but furthermore preserved mental structure and reduced inflammation.
Lemborexant-treated mice had 40 % more brain size than controls who had not received it or who had received a different sleep aid. Notably, these neuroprotective effects were only observed in female mice, which may be a sign of sex differences in the severity of tau pathology.
Important Information
- Upregulation: Male mice’s lemborexant reduced tau concentration and mind body death.
- Careful System: Just sleep aids that block orexin receptors, such as lemborexant, demonstrated benefits.
- Fundamental protection: Treated animals had significantly larger brain volumes, a region essential to memory.
Origin: WUSTL
According to new studies from Washington University School of Medicine in St. Louis, a common sleep aid promotes healthy sleep habits and protects animals from head injury caused by neurological disorders like Alzheimer’s condition.
Lemborexant, a drug that lowers the risk of an unnatural form of a protein called tau from growing in the brain, lowers the aggressive brain damage that tau is known to cause in Alzheimer’s.
The research suggests that lemborexant and other similar medications, such as lemborexants, could be used to treat or stop the tau-related damage that is present in various neurological conditions, including Alzheimer’s, liberal supranuclear paralysis, corticobasal symptoms, and some frontotemporal dementias.
The study was published in Nature Science on May 27.
The Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology at WashU Medicine, David M. Holtzman, MD, said,” We have known for a long time that sleep loss is a risk factor for Alzheimer’s disease.
We have demonstrated in this new study that lemborexant promotes sleep and reduces excessive tau, which is believed to be a major contributor to the neurological damage seen in Alzheimer’s and other related disorders.
We are optimistic that this finding may lead to further research into this sleep aid and the development of novel therapies that may outweigh present possibilities, either alone or in combination with other treatments currently available.
The antibodies to amyloid that we currently use to treat patients with early, mild Alzheimer’s dementia are helpful, but they don’t as much as we would like, he said.
This type of sleep aid is worthwhile looking into further because we need ways to reduce the abnormal tau buildup and its accompanying inflammation. We’re interested in whether pursuing both amyloid and tau with a combination of therapies will slow or stop the progression of this disease.
One of the first to link the development of proteins like amyloid and tau with poor sleep as a risk factor for Alzheimer’s disease and Holtzman and his team made the discovery that poor sleep was a key factor in Alzheimer’s disease.
Previous research on mice that are genetically susceptible to the amyloid and tau buildup that are found in Alzheimer’s disease demonstrated that sleep deprivation worsens this buildup. According to the most recent study, improving sleep in these mice with lemborexant appeared to be protective, with less buildup of tau protein tangles and less nerve cell death as a result of Alzheimer’s disease.
In a number of neurological conditions, including Alzheimer’s, the protein tau accumulates in the brain, leading to inflammation and the death of brain cells. Lemborexant was tested in part by Holtzman and his team, which was co-led by first author Samira Parhizkar, PhD, a neurology instructor. Its effects are known to be impacted by abnormal tau accumulation in some areas of the brain.
It also doesn’t interfere with motor coordination, which is a concern for those who use hypnotic sleep aids and those with dementia.
Lemborexant is one of three sleep medications that has the approval of the Food and Drug Administration that acts as orexin receptor antagonists in an effort to stop the action of orexins, small proteins that regulate sleep. Lemborexant blocks both type 1 and type 2 orexin receptors.
Receptors are proteins that bind to other molecules and control cell activity on the cell surface. These receptors are well known to be involved in a variety of physiological processes, including sleep-wake cycles and appetite.
As part of a , a research collaboration with WashU Medicine , which aimed to create novel treatments for Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases, Eisai Pharmaceuticals provided lemborexant for these studies.
Lemborexant reduced brain damage in mice that are genetically susceptible to harmful tau buildup compared to control mice. For instance, those taking lemborexant displayed 30 % to 40 % more of a larger volume in the hippocampus, which is crucial for memory formation, than control mice and those taking zolpidem, a sleep aid from a different class of drugs.
Zolpidem made it easier to sleep but did not prevent tau accumulation in the brain like lemborexant did, suggesting that the type of sleep aid, orexin receptor antagonist, is essential to producing the neuroprotective effects.
The researchers are still trying to understand why the beneficial effects were only observed in male mice.
Normal tau is crucial for maintaining neuronal structure and function. When it is healthy, it carries a small number of chemical tags known as phosphate groups. However, it can clump together when tau accumulates too many of these chemical tags, causing nerve cell death and inflammation.
The authors discovered that lemborexant prevents excess tags from being added to tau by blocking orexin receptors, aiding in tau maintaining its healthy functions in the brain.
Holtzman stated that his team is still looking into the causes of the only male mice benefit from lemborexant treatment.
He questioned whether the sex discrepancy could be brought on by the observation that male mice with the same genetic predisposition to tau accumulation had less severe neurodegeneration than female mice with the same genetic predisposition. Potential beneficial effects of the drug could have been smaller and more difficult to detect because there was less damage to begin with.
Funding: This work was supported by the National Institutes of Health ( NIH), grant numbers P01NS074969, RF1NS090934, and RF1AG061776, the JPB Foundation, the Alzheimer’s Association, grant number AARF-21-850865, the Rainwater Foundation, and a COBRAS Feldman Fellowship.
Holtzman is the inventor of a patent allowing C2N Diagnostics to use anti-tau antibodies for therapeutic purposes. Halltzman cofounded C2N Diagnostics and sits on its scientific advisory board.
About this research in neuropharmacology and Alzheimer’s disease
Author: Jessica Church
Source: WUSTL
Contact: Jessica Church – WUSTL
Image: The image is credited to Neuroscience News
Original research has been made private.
In a mouse model of tauopathy, David M. Holtzman and colleagues ‘ study,” Lemborexant ameliorates tau-mediated sleep loss and neurodegeneration in males.” Neuroscience of the natural world
Abstract
In a mouse model of tauopathy, lemborexant ameliorates neurodegeneration and sleep loss in males.
The pathogenesis of neurodegenerative diseases like Alzheimer’s disease and primary tauopathies are linked to sleep disturbances.
We show that the P301S/E4 mouse model of tauopathy, which has a dual orexin receptor antagonist, lemborexant, ameliorates tau-associated sleep-wake behavior impairments.
By preventing abnormal tau phosphorylation, it also protects male P301S/E4 mice from chronic reactive microgliosis and brain atrophies.
After taking the nonorexinergic drug zolpidem, which similarly promoted nonrapid eye movement sleep, these neuroprotective effects did not appear in males.
Additionally, phosphorylated tau in the brain of wild-type mice was reduced by both genetically altered orexin receptor 2 and lemborexant treatment.
These findings suggest that orexin receptor antagonism may be effective for preventing abnormal tau phosphorylation and limiting tau-induced damage in the treatment of sleep.
