Protein reduces levels of amyloid beta and tau hyperphosphorylation, 2 hallmarks of Alzheimer's
Investigators at Burnham Institute for Medical Research (Burnham) and colleagues have identified a novel mouse gene (Rps23r1) that reduces the accumulation of two toxic proteins that are major players in Alzheimer's disease: amyloid beta and tau. The amyloid and tau lowering functions of this gene were demonstrated in both human and mouse cells. Amyloid beta is responsible for the plaques found in the brains of Alzheimer's patients. Tau causes the tangles found within patients' brain cells. The study was published in the journal Neuron on November 12. These findings could lead to new treatments for Alzheimer's disease.
Scientists throughout the world are searching for ways to reduce the levels of these two proteins as a means of treating Alzheimer's, so finding a gene that can control the amount of both proteins is particularly important. Overproduction of amyloid beta and its accumulation within senile plaques in the brain and the formation of abnormal tau tangles (neurofibrillary tangles composed of hyperphosphorylated tau protein) are major causes of disrupted brain function in Alzheimer's disease. Hauxi Xu, Ph.D., professor and acting director of the Neurodegenerative Disease Research program at Burnham, collaborated with Nobel laureate Paul Greengard, Ph.D., of the Laboratory of Molecular and Cellular Neuroscience at The Rockefeller University, Stanley Cohen, Ph.D., of the Department of Genetics at Stanford University School of Medicine, Limin Li, Ph.D., of Functional Genetics, Inc., and with researchers from Xiamen University, to demonstrate that the RPS23R1 protein, which is encoded by the gene, triggers a signaling pathway within brain cells that inhibits a protein called GSK-3 (glycogen synthase kinase-3), which regulates both amyloid beta generation and tau phosphorylation (required for tangle formation).