mTOR signaling as a molecular target for the alleviation of Alzheimer's disease pathogenesis

• Published in: Neurochemistry international 2022-05, Vol.155, p.105311-105311, Article 105311
• Main Authors: Rapaka, Deepthi, Bitra, Veera Raghavulu, Challa, Siva Reddy, Adiukwu, Paul C.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Apoptosis; Autophagy; Cognition; Humans; Macroautophagy; Mammals - metabolism; mTOR; Rapamycin; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2022.105311

Mechanistic/mammalian target of rapamycin (mTOR) belongs to the phosphatidylinositol kinase-related kinase (PIKK) family. mTOR signaling is required for the commencement of essential cell functions including autophagy. mTOR primarily governs cell growth in response to favourable nutrients and other growth stimuli. However, it also influences aging and other aspects of nutrient-related physiology such as protein synthesis, ribosome biogenesis, and cell proliferation in adults with very limited growth. The major processes for survival such as synaptic plasticity, memory storage and neuronal recovery involve a significant mTOR activity. mTOR dysregulation is becoming a prevalent motif in a variety of human diseases, including cancer, neurological disorders, and other metabolic syndromes. The use of rapamycin to prolong life in different animal models may be attributable to the multiple roles played by mTOR signaling in various processes involved in ageing, protein translation, autophagy, stem cell pool turnover, inflammation, and cellular senescence. mTOR activity was found to be altered in AD brains and rodent models, supporting the notion that aberrant mTOR activity is one of the key events contributing to the onset and progression of AD hallmarks This review assesses the molecular association between the mTOR signaling pathway and pathogenesis of Alzheimer's disease. The research data supporting this theme are also reviewed. [Display omitted] •mTOR signaling is associated with Alzheimer's disease pathogenesis.•Increased mTOR signaling contributes to tau aggregation, inflammation, and elevated oxidative stress.•mTOR activation increases cholinesterase levels and contributes to cognitive dysfunction.•Rapamycin improves cognitive dysfunctions and clears amyloid and tau aggregates.