Novel mouse gene could lead to new Alzheimer’s treatments

WASHINGTON - Scientists 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 shown in both human and mouse cells.

Amyloid beta is responsible for the plaques found in the brains of Alzheimer’s patients while Tau causes the tangles found within patients’ brain cells.

According to researchers at Burnham Institute for Medical Research (Burnham), their findings could lead to new treatments for Alzheimer’s disease.

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, from Burnham Institute, and colleagues showed 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.

The team also found that the Rps23r1 gene, whose human counterpart has not yet been identified, was created through a process called retroposition, in which a gene is duplicated through the reverse transcription (or reading) of mRNA and the duplicate is placed in a different location in the cell’s DNA.

Although most retroposition events result in non-functional duplicates (called pseudogenes), in rare cases, retroposed genes, like Rps23r1, can become functional.

“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,” Dr. Xu said.

The study was published in the journal Neuron on November 12. (ANI)