Rheb protein depletion leads to memory loss

Scientists from The Scripps Research Institute (TSRI) have made an essential discovery to drug development when they discovered a way to treat age-related memory loss in conditions like Alzheimer's through Rheb protein. They discovered that decreased levels of a Rheb protein leads to memory loss in animal models and are connected to elevated levels of BACE1 in the brain, as discovered in autopsies of patients with Alzheimer's disease.

Srinivasa Subramaniam who serves as an Associate Professor at TSRI led this study, which was published in the Neurobiology of Aging journal ahead of print.

Rheb and Alzheimer’s

In the recent study, researchers investigated the connection between Rheb and BACE1 enzyme. BACE1 levels are elevated in aged people and patients with Alzheimer’s.

Subraminam remarked, We know that BACE1 is regulated by Rheb. BACE1 is a main drug target in Alzheimer's. Studies of brain autopsies of patients who suffered from Alzheimer's have shown a remarkable decrease in Rheb, hence, it is promising that a raise in Rheb levels might revert the buildup of amyloid plaques or facilitate a decrease or even revert age-related memory loss.”

To discover the effect of removing Rheb, Subramaniam's team placed genetically-altered mice on a series of behavior analyses starting at six months of age.

Rheb removal had no effect on body weight or motor activity of the mice, but has slight and discerning changes on some memory-based activities like memory recall and navigating a maze. Subramaniam and his colleagues analogized these symptoms to memory loss that was found in humans with dementia and Alzheimer's.

They also discovered that Rhed reduction elevated the levels of BACE1 enzyme, which was constant with earlier research demonstrating that elevated BACE1 may be a causative agent for memory loss.

As previous research in fruit flies have shown that, protein starvation may stimulate Rheb mRNA, Subramaniam's team claimed that a high-protein intake could be a risk factor for Rheb depletion with age, further leading to mild to severe cognitive deficiency in humans, as observed in animal models.

This indicates that nutrient signaling in mammals could control cognitive functions by altering Rheb-BACE1 pathway, Subramaniam noted.

Neelam Shahani, the first author of the study mentioned, “On the whole, our study shows that forebrain Rheb reduction favors aging-related cognitive disorders. Rheb pathway could be a target and could provide therapeutic potential for age-related or Alzheimer’s disease-related memory loss.”