Mammalian Target of Rapamycin (mTor) Mediates Tau Protein Dyshomeostasis

Abstract

Background: Perturbations of the mammalian target of rapamycin (mTor) signaling pathway are implicated in Alzheimer disease (AD). Results:The activated mTor alters the activity of major tau kinases contributing to the formation of tau dyshomeostasis. Conclusion:We established a cellular system using genetic activation of mTor that developed authentic AD-like changes. Significance: The study provides potential tools for identifying tau-based therapeutics.

Functional Role of RNA Polymerase II and P70 S6 Kinase in KCl Withdrawal-induced Cerebellar Granule Neuron Apoptosis

“…Therefore, it is possible that targeted inhibition of CDK9, CDK7, P70S6K, or the specific mRNAs regulated by P70S6K may prevent neuronal loss. On the basis of our data and the finding that P70S6K activation induces Tau hyperphosphorylation and tangle formation (65,72), we hypothesize that inhibition of P70S6K may not only prevent apoptosis but also protect neurons from microtubule destabilization and neurodegeneration. An identification of the mRNAs regulated by P70S6K may provide us with more insights into their role in apoptosis, and these mRNAs could be targeted to prevent neurodegeneration and neuronal loss associated with various neurodegenerative diseases.…”

Genetic Reduction of Mammalian Target of Rapamycin Ameliorates Alzheimer's Disease-Like Cognitive and Pathological Deficits by Restoring Hippocampal Gene Expression Signature

“…Data are presented as means Ϯ SEM and were analyzed by one-way ANOVA; *p Ͻ 0.05. Caccamo et al, 2013;Tang et al, 2013). Thus, mTOR might represent a molecular link between A␤ accumulation and tau pathology.…”

Targeting Unselective Autophagy of Cellular Aggregates

“…It acts in vitro as expected from an mTORC1 inhibitor on tau phosphorylation [75][76][77]. Rapamycin decreases tau levels (total and phosphorylated) in a cellular assay [78], possibly acting on translation and autophagy. It reduces tau neurotoxicity in R406W mutant tau-carrying Drosophila flies [47].…”