BIMR LogoScientists at Burnham Institute for Medical Research, Burnham are believed to have recognized a new mouse gene Rps23r1 that reduces the accumulation of two toxic proteins. Apparently, these toxic proteins namely amyloid beta and tau are major players in Alzheimer’s disease. The findings could perhaps lead to novel treatments for Alzheimer’s disease.

The amyloid and tau lowering functions of this gene appear to have been recognized in both human and mouse cells. Amyloid beta is known to be responsible for the plaques found in the brains of Alzheimer’s patients. Whereas tau seems to cause the tangles found within patients’ brain cells.

Scientists all over the world are investigating ways to decrease the levels of these two proteins as a means of treating Alzheimer’s. Thus finding a gene that may be able to control the amount of both proteins is particularly essential.

Overproduction of amyloid beta and its accumulation inside senile plaques in the brain and the formation of abnormal tau tangles appear to be major causes of disrupted brain function in Alzheimer’s disease. Abnormal tau tangles are known to be neurofibrillary tangles which are composed of hyperphosphorylated tau protein.

Hauxi Xu, Ph.D., professor and acting director of the Neurodegenerative Disease Research program at Burnham said that, “From the point of view of treating Alzheimer’s disease, if we can express the mouse gene in human brain cells, we may be able to control the buildup of amyloid beta and tau neurofibrillary tangles. From an evolutionary point of view, we have found an example of a retroposed gene that took on a completely new function.”

During the study, Dr. Xu along with his colleagues were noted to have made use of a technology called random homozygous gene perturbation to search for genes that regulate amyloid beta generation. This allowed the team to recognize the Rps23r1 gene. Further, they found that the RPS23R1 protein encodes may be able to interact with a protein called adenylate cyclase. Adenylate cyclase seems to stimulate a second protein called protein kinase A, which inhibits GSK-3 activity.

The effects of RPS23R1 on reducing amyloid beta levels and tau phosphorylation appear to have been confirmed in a transgenic Alzheimer’s disease mouse model. The team then determined that Rps23r1 seems to be a reverse-transcribed version of the mouse ribosomal protein S23 (Rps23) gene, which is almost identical to the human Rps23 gene.

The authors have shown that the RPS23R1 protein, which is encoded by the gene, seems to trigger a signaling pathway within brain cells that inhibits a protein called glycogen synthase kinase-3 (GSK-3). Supposedly, GSK-3 regulates both amyloid beta generation and tau phosphorylation that is needed for tangle formation.

The team also found that the Rps23r1 gene appears to have been formed via a process called retroposition. It was observed that Rps23r1 genes’ human counterpart has not yet been recognized. In this process, a gene could perhaps be duplicated through the reverse transcription or reading of mRNA. More so, the duplicate appears to have been placed in a different location in the cell’s DNA. Though most retroposition events lead to non-functional duplicates called pseudogenes, in unusual cases, retroposed genes, like Rps23r1, may become functional.

The findings of the study have been published in the journal, Neuron.