ReviewFrontiers in pharmacology2024
Pharmacological mTOR inhibitors in ameliorating Alzheimer's disease: current review and perspectives.
Review in Frontiers in pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Betulinaldehyde Ameliorates Aβ-Induced Neurotoxicity and Cognitive Deficits by Modulating the eEF2K/eEF2 Pathway.CNS neuroscience & therapeutics · 2026Article
- Rewiring mTOR signaling in Alzheimer's disease: emerging mTOR modulators beyond oncology.Bioscience reports · 2026Review
- Trends and Research Frontiers in Mammalian Target of Rapamycin and Alzheimer's Disease.Molecular neurobiology · 2026Review
- Critical Roles and Molecular Mechanisms of Chaperone-Mediated Autophagy in Infections.International journal of molecular sciences · 2026Review
- Discontinued BACE1 Inhibitors in Phase II/III Clinical Trials and AM-6494 (Preclinical) Towards Alzheimer's Disease Therapy: Repurposing Through Network Pharmacology and Molecular Docking Approach.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The Role of TFEB-Regulated Autophagy in Intervertebral Disc Degeneration and Its Therapeutic Potential.Journal of inflammation research · 2026Review
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- Repeated Exposure to Lidocaine Induces Alzheimer's‐Like Cognitive Impairment and Neuropathology in Aged Mice Through BDNF‐Regulated Autophagy.Journal of cellular and molecular medicine · 2025Article
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Genetic and Pathogenic Overlaps Between Autism Spectrum Disorder and Alzheimer's Disease: Evolutionary Features and Opportunities for Drug Repurposing.International journal of molecular sciences · 2025Article
- Preclinical Evaluation of mTORC1 Inhibition via Rapamycin in Machine-Perfused Rodent Livers.Research square · 2025Article
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- The Inflammatory Nexus: Unraveling Shared Pathways and Promising Treatments in Alzheimer's Disease and Schizophrenia.International journal of molecular sciences · 2025Review
- The Role of S6K1 in Aging and Alzheimer's Disease: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Genetically encoded biosensors of metabolic function for the study of neurodegeneration, a review and perspective.Neurophotonics · 2025Review
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- Biomarkers in glioblastoma and degenerative CNS diseases: defining new advances in clinical usefulness and therapeutic molecular target.Frontiers in molecular biosciences · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Traditionally, pharmacological mammalian/mechanistic targets of rapamycin (mTOR) kinase inhibitors have been used during transplantation and tumor treatment. Emerging pre-clinical evidence from the last decade displayed the surprising effectiveness of mTOR inhibitors in ameliorating Alzheimer's Disease (AD), a common neurodegenerative disorder characterized by progressive cognitive function decline and memory loss. Research shows mTOR activation as an early event in AD development, and inhibiting mTOR may promote the resolution of many hallmarks of Alzheimer's. Aberrant protein aggregation, including amyloid-beta (Aβ) deposition and tau filaments, and cognitive defects, are reversed upon mTOR inhibition. A closer inspection of the evidence highlighted a temporal dependence and a hallmark-specific nature of such beneficial effects. Time of administration relative to disease progression, and a maintenance of a functional lysosomal system, could modulate its effectiveness. Moreover, mTOR inhibition also exerts distinct effects between neurons, glial cells, and endothelial cells. Different pharmacological properties of the inhibitors also produce different effects based on different blood-brain barrier (BBB) entry capacities and mTOR inhibition sites. This questions the effectiveness of mTOR inhibition as a viable AD intervention strategy. In this review, we first summarize the different mTOR inhibitors available and their characteristics. We then comprehensively update and discuss the pre-clinical results of mTOR inhibition to resolve many of the hallmarks of AD. Key pathologies discussed include Aβ deposition, tauopathies, aberrant neuroinflammation, and neurovascular system breakdowns.
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