BrightFocus-Funded Discovery Could Lead to Drugs that Slow Alzheimer's Disease Progression
Targeting ROCK2 protein reduces beta-amyloid by relocating a key disease-causing protein. Source: Journal of Neuroscience.
This research was supported by BrightFocus
BrightFocus-funded researcher, Jeremy Herskowitz, Ph.D., has identified a new way to shut down the production of toxic beta-amyloid by relocating a key amyloid-producing protein, called BACE, into another part of the cell where it can do less harm. This indirect way of blocking BACE was accomplished by reducing levels of a brain protein, called ROCK2, which is normally involved with controlling cell movement and shape. The researchers found that they could reduce beta-amyloid when their drug was added to cultured brain cells and when injected directly into the brains of mice designed to show features of Alzheimer’s disease.
There are currently no disease-modifying drugs available for patients with Alzheimer’s disease. A future indirect ROCK2-targeting strategy could not only reduce the production of beta-amyloid, but avoid the toxic side effects that may be seen by other researchers directly targeting BACE and other key proteins. The next step for these researchers will be to deliver this drug by mouth or bloodstream into Alzheimer’s disease mice to confirm whether these biochemical effects translate into the reduction of cognitive issues.
Amyloid is a general term for protein fragments that the body produces normally. Beta amyloid is a protein fragment snipped from an amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques.