Targeting RhoA signaling as Therapeutic strategy for Alzheimer's disease

RhoA is a protein found in many cells and which is a key molecule in many biological pathways. Recent studies have shown that RhoA may also play a role in mediating some of the toxic effects of beta-amyloid in the brain. Beta-amyloid, is a protein fragment that forms clumps known as amyloid plaques, one of the characteristic features of Alzheimer’s disease in the brain. In the early stages of Alzheimer’s disease, the clumping of beta-amyloid has a toxic effect and can result in the loss of synapses. Synapses are specialized structures through which nerve cells communicate with other nerve cells. Synaptic function is essential for many of the unique capabilities of the brain, including learning and memory. There is evidence that some of the damaging effects of beta-amyloid on synapses may be mediated through RhoA activity. Roger Lefort, Ph.D., and colleagues have found evidence that inhibition of RhoA may help preserve synaptic function in nerve cells exposed to beta-amyloid. They hypothesize that by blocking the activity of RhoA, they can prevent damage and loss of synapses even if beta-amyloid is present. They have proposed a series of experiments to test if a drug that leads to inhibition of RhoA activity can protect nerve cells exposed to beta-amyloid. The researchers will perform these studies in nerve cells growing in laboratory dishes, as well as in mice genetically altered to have an Alzheimer’s-like condition. These studies will explore a potential treatment strategy for slowing or halting the effects of the Alzheimer’s disease process on brain synapses.