Sleep Aid Lemborexant Demonstrates Neuroprotective Effects in Mice

A recent study conducted by researchers at Washington University School of Medicine in St. Louis has revealed that a common sleep medication, lemborexant, not only improves sleep patterns but also offers protection against neurodegenerative damage in mice. The research shows that the drug can prevent the harmful accumulation of tau protein—a hallmark of diseases like Alzheimer’s—and reduce associated brain inflammation.

This groundbreaking discovery suggests that drugs acting as orexin receptor antagonists, like lemborexant, could play a crucial role in treating or preventing neurodegenerative disorders characterized by tau buildup, such as Alzheimer's disease, progressive supranuclear palsy, corticobasal syndrome, and certain frontotemporal dementias. The study's findings were published in the journal Nature Neuroscience.

The team, led by senior author Dr. David M. Holtzman, emphasized the longstanding link between sleep disturbances and an increased risk of Alzheimer’s. Their experiments with genetically predisposed mice demonstrated that lemborexant enhances sleep quality and significantly decreases abnormal tau accumulation. Notably, mice treated with lemborexant exhibited larger hippocampal volume—a brain region critical for memory—and reduced brain tissue gaps, compared to untreated controls.

Interestingly, the protective effects were observed only in male mice. Researchers are investigating the reasons behind this sex-specific response, noting that female mice with similar genetic risks showed less neurodegeneration, which might influence the drug's efficacy.

Mechanistically, the study explains that tau proteins normally support neuron structure, but when overly tagged with phosphate groups, they form tangles that trigger inflammation and nerve cell death. Lemborexant appears to inhibit this pathological tagging by blocking orexin receptors, thereby helping tau maintain its normal function.

The drug’s impact extends beyond tau, as improved sleep may indirectly reduce the inflammation and neuronal loss characteristic of Alzheimer’s pathology. This research advocates for further exploration into combining sleep aids like lemborexant with existing treatments that target amyloid proteins, potentially offering a more comprehensive approach to slowing disease progression.

Holtzman’s team highlighted that their prior work linked sleep deprivation with increased protein buildup in the brain. The current findings suggest that proper sleep management through orexin receptor antagonists could be a novel strategy to combat neurodegeneration. Future studies aim to verify whether these benefits can translate into humans, offering hope for new therapeutic options for Alzheimer’s and related disorders.

For more detailed information, refer to the original study: Nature Neuroscience.