DEC 07, 2016 7:59 AM PST

Scripps Florida Scientists Uncover Potential Driver of Age- and Alzheimer's-Related Memory Loss


JUPITER, FL – December 7, 2016 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have made an important discovery toward the development of drugs to treat age-related memory loss in diseases like Alzheimer’s. They found that reduced levels of a protein called Rheb result in spontaneous symptoms of memory loss in animal models and are linked to increased levels of another protein known to be elevated in the brains of Alzheimer’s disease patients.

Their study, led by TSRI Associate Professor Srinivasa Subramaniam, was published recently online ahead of print in the journal Neurobiology of Aging.
 

Link to Known Alzheimer’s Trigger


In the new study, Subramaniam’s group investigated the link between Rheb and an important enzyme called BACE1, which is elevated in older adults and people with Alzheimer’s disease.

“We know that Rheb regulates BACE1, which is a major drug target in Alzheimer’s disease,” Subramaniam said. “Studies of the autopsied brains of Alzheimer’s patients have found a significant reduction in Rheb, so it is possible that an increase in Rheb could reverse the buildup of amyloid plaque or help reduce or even reverse age-related memory loss.”

To uncover the impact of eliminating Rheb, Subramaniam and his colleagues put genetically altered mice through a battery of behavior tests beginning at around six months of age.

While Rheb depletion did not affect the overall body weight or motor activity of the animals, it did have subtle and selective effects on certain memory tasks they performed, such as navigating a maze and memory recall. The researchers compared these symptoms to memory deficits that occur in humans with Alzheimer’s disease and related dementia.

They also found that Rheb depletion increased BACE1 levels, which was consistent with previous research showing that higher BACE1 levels may be a contributing factor for memory deficits.

The fact that some research shows that Rheb messenger RNA is induced during protein starvation in fruit flies, led Subramaniam and his colleagues to theorize that a high-protein diet in humans might be a risk factor for decreasing Rheb levels with age, resulting in mild-to-severe cognitive deficits, as seen in animal models.

“This is an indication that nutrient signaling might regulate cognitive functions in mammals through alteration of Rheb–BACE1 pathway activity,” Subramaniam said.

“Overall, our study demonstrates that forebrain Rheb depletion promotes aging-associated cognitive defects,” said Neelam Shahani, the first author of the study. “Targeting the Rheb pathway may offer some therapeutic potential for aging- or Alzheimer’s disease-associated memory deficits.”

In addition to Subramaniam and Shahani, other authors of the study, “Forebrain Depletion of Rheb GTPase Elicits Spatial Memory Deficits in Mice,” are TSRI’s Wen-Chin Huang, Megan Varnum and Damon T. Page.

This work was supported by the National Institutes of Health (grants NIH/NINDS R01-NS087019, NIH/NINDS R01-NS094577, and NIH/NIMH R01-MH105610), Ms. Nancy Lurie Marks and the Alzheimer’s Disease Association (grant 2015-NIRG-344356).

This article was originally published on Scripps.edu.
About the Author
  • The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists-including two Nobel laureates-work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
You May Also Like
DEC 17, 2020
Genetics & Genomics
Using Tomatoes to Produce a Parkinson's Drug
DEC 17, 2020
Using Tomatoes to Produce a Parkinson's Drug
More and more people are being diagnosed with Parkinson's disease as the world's population ages. Scientists have now en ...
JAN 01, 2021
Genetics & Genomics
Common Brain Disorder Has a Genetic Influence
JAN 01, 2021
Common Brain Disorder Has a Genetic Influence
It's thought that as many as one in one hundred people are born with a brain disorder known as Chiari 1 malformation, bu ...
JAN 05, 2021
Cell & Molecular Biology
Brown Fat Appears to Protect Against Disease
JAN 05, 2021
Brown Fat Appears to Protect Against Disease
Not all fat is the same. White fat is what we're usually thinking of when we think of flabby tissue that stores excess c ...
JAN 06, 2021
Genetics & Genomics
Junk DNA Helps Control the Body Clock
JAN 06, 2021
Junk DNA Helps Control the Body Clock
Our bodies run on a kind of molecular clock, which helps regulate and time certain functions beyond just waking and slee ...
JAN 18, 2021
Cell & Molecular Biology
MicroRNAs May be Treatment Targets for Traumatic Brain Injury
JAN 18, 2021
MicroRNAs May be Treatment Targets for Traumatic Brain Injury
Traumatic brain injury, which can happen after a blow to the head, has been called a silent epidemic and is the number o ...
JAN 20, 2021
Microbiology
Cannabis Compound Could Lead to New Class of Antibiotics
JAN 20, 2021
Cannabis Compound Could Lead to New Class of Antibiotics
For the first time, a synthetic version of a non-psychoactive molecule found in marijuana has been shown to kill pathoge ...
Loading Comments...