mTOR signaling as a molecular target for the alleviation of Alzheimer's disease pathogenesis
Deepthi Rapaka1, Veera Raghavulu Bitra2, Siva Reddy Challa3
1A.U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 530003, India.
Abstract:
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.
Insights
Mammalian target of rapamycin (mTOR) signaling impacts cell growth, aging, and neuronal functions. Aberrant mTOR activity is linked to Alzheimer's disease progression, suggesting therapeutic potential.
Area of Science:
- Molecular Biology
- Cellular Biology
- Neuroscience
Background:
- Mammalian target of rapamycin (mTOR) is a key PIKK family kinase regulating cell growth, autophagy, and nutrient sensing.
- mTOR signaling influences vital cellular processes including protein synthesis, ribosome biogenesis, and proliferation.
- Dysregulation of mTOR is implicated in various diseases like cancer, metabolic syndromes, and neurological disorders.
Purpose of the Study:
- To review the molecular association between the mTOR signaling pathway and Alzheimer's disease (AD) pathogenesis.
- To examine research data supporting the role of mTOR in AD development and progression.
Main Methods:
- Literature review of studies investigating mTOR signaling in AD.
- Analysis of molecular mechanisms linking mTOR to AD hallmarks.
Main Results:
- mTOR activity is altered in Alzheimer's disease brains and relevant animal models.
- Aberrant mTOR signaling is a significant factor in the onset and progression of AD.
Conclusions:
- The mTOR pathway is critically involved in the pathogenesis of Alzheimer's disease.
- Understanding the mTOR-AD connection may reveal new therapeutic strategies for neurodegenerative diseases.
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