Protein behind Alzheimer's spread found

Indian-origin scientists have found for the first time that declining levels of a protein in the brain may play a key role in the advance of Alzheimer's disease.
The new study from the Florida campus of The Scripps Research Institute, US, identified a critical regulator of a molecule deeply involved in the progression of Alzheimer's disease.
The regulator is known as Rheb, a protein that many believe may be active in neural plasticity, the ability of the brain to change in response to learning.
The scientists found that Rheb binds and regulates activity of a molecule known as BACE1, an important enzyme in Alzheimer's disease pathology, establishing for the first time a new molecular link between Rheb and BACE1.

"We found that Rheb regulates BACE1, which is a major drug target in Alzheimer's disease," said Srini Subramaniam, a TSRI biologist who led the study.
"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," said Subramaniam.

The study noted that in some genetically modified animal models, an increase of Rheb has already been shown to reduce BACE1 levels and the production of amyloid plaque.
"If we can uncover the mechanism by which Rheb alters BACE1 levels, that would be a very good drug target," said Neelam Shahani, a first author of the study with William Pryor, both research associates in the Subramaniam lab.

The new study indicates that Rheb degrades BACE1 through a number of pathways, but more research needs to be done before drug candidates can be developed.
"We're very interested in the disease process and plan to keep moving forward to understand precisely how Rheb regulates BACE1," said Pryor.
The study was published in the Journal of Biological Chemistry.