Rapamycin is also known as sirolimus and is sold under the brand name Rapamune.
An innovative strategy to lessen the plaques was also found in the study.
The oral administration of rapamycin to an Alzheimer’s disease mouse model induces an increase in beta (β)-amyloid protein plaques, according to researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio). β-amyloid buildup is a hallmark of Alzheimer’s disease.
Rapamycin is FDA-approved for the treatment of transplant and cancer patients. The drug is also referred to as sirolimus and is sold under the name Rapamune. Publicly available data suggest that the drug might also improve learning and memory in aged mice. According to publicly accessible evidence, the medication may also boost learning and memory in elderly mice. The UT Health San Antonio researchers, on the other hand, discovered that following rapamycin administration, a protein called Trem2 (triggering receptor expressed on myeloid cells 2) is drastically reduced. Trem2 is found in microglia, immune cells found in the brain and spinal cord.
“Trem2 is a receptor located on the surface of the microglia, and it enables these cells to engulf and degrade β-amyloid,” said study senior author Manzoor Bhat, Ph.D. “Loss of Trem2 in microglia impairs the vital function of amyloid degradation, which in turn causes a buildup of β-amyloid plaques.” Dr. Bhat is professor and chairman of the Department of Cellular and Integrative Physiology at UT Health San Antonio and vice dean for research in the university’s Joe R. and Teresa Lozano Long School of Medicine.
Drug target
Importantly, the study, recently published in the Journal of Neuroscience, also featured a novel way to increase Trem2 in microglia. When the study lead author, Qian Shi, PhD, assistant professor in the Department of Cellular and Integrative Physiology, deleted a gene called Tsc1 from the microglia, there was a marked increase in Trem2 levels and a decrease in β-amyloid plaques.
Previous research has shown that loss of Tsc1 leads to activation of the mTOR (mammalian target of rapamycin) signaling pathway. Rapamycin, in contrast, blocks this pathway. “We expected that selective loss of Tsc1, only in microglia and not in neurons or other cells, would have negative consequences because inhibiting mTOR with rapamycin has known therapeutic uses in some disease models,” Dr. Shi said. “But the opposite was occurring.” Thus, repressing Tsc1 solely in microglia to enhance β-amyloid uptake could be a potential drug target, Dr. Shi said. READ MORE...
