Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in the <i>5XFAD</i> Alzheimer's Disease Model
Qian Shi, Cheng Chang, Afaf Saliba, Manzoor A. Bhat
Abstract
evidence that mTOR activation in microglia would benefit β-Amyloid (Aβ)-related AD pathologies, as it upregulates Trem2, a key receptor for Aβ plaque uptake. Inhibition of mTOR pathway with rapamycin, a well-established immunosuppressant, downregulated Trem2 in microglia and reduced Aβ plaque clearance indicating that mTOR inactivation may be detrimental in Aβ-associated AD patients. This finding will have a significant public health impact and benefit, regarding the usage of rapamycin in AD patients, which we believe will aggravate the Aβ-related AD pathologies.
Topics & Concepts
MicrogliaPI3K/AKT/mTOR pathwayTREM2TSC1Downregulation and upregulationCell biologymTORC1Mechanistic target of rapamycinChemistryPhagocytosisCancer researchBiologySignal transductionImmunologyInflammationBiochemistryGeneNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNuclear Receptors and Signaling