mTOR: Central to Health, Disease, and Therapy

Hugo Lefevre^*
*Correspondence: Hugo Lefevre, Department of Neurophysiology, University of Lyon, Lyon, France, Email:

Introduction

This article explores the mTOR pathway's critical involvement in cancer development, detailing its pathophysiological mechanisms. It highlights how dysregulation of mTOR promotes tumor growth, proliferation, and survival. The authors also discuss various therapeutic strategies targeting this pathway, emphasizing the potential of mTOR inhibitors in cancer treatment and outlining future directions for drug development.[1] This review elucidates the crucial role of mTOR signaling in regulating various metabolic processes, including glucose, lipid, and protein metabolism. It delves into how mTOR dysregulation contributes to metabolic diseases like obesity, type 2 diabetes, and non-alcoholic fatty liver disease. The article emphasizes the complex interplay between mTOR and cellular energy status, offering insights into potential therapeutic targets for metabolic disorders.[2] This article examines the profound impact of the mTOR pathway on the aging process and age-related diseases. It discusses how modulating mTOR activity, particularly through its inhibition, can extend lifespan and healthspan in various organisms. The authors review current therapeutic strategies, such as rapamycin and its analogs, and explore emerging approaches for targeting mTOR to combat aging and associated pathologies, providing insights into future research directions.[3] This article investigates the intricate reciprocal regulation between the mTOR pathway and autophagy, a fundamental cellular recycling process. It details how mTOR acts as a central negative regulator of autophagy, sensing nutrient availability to control catabolic and anabolic processes. The authors discuss the implications of this interplay in various physiological contexts and pathological conditions, including cancer, neurodegenerative diseases, and metabolic disorders, highlighting its therapeutic potential.[4] This review investigates the promising therapeutic potential of targeting the mTOR signaling pathway in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease. It highlights how mTOR dysregulation contributes to neuronal dysfunction, protein aggregation, and impaired autophagy, key pathological hallmarks of these conditions. The authors discuss various pharmacological and non-pharmacological interventions aimed at modulating mTOR activity to mitigate disease progression and improve neuronal health.[5] This review explores the multifaceted role of the mTOR pathway in regulating immune cell function and its growing importance in immunotherapy. It describes how mTOR controls the differentiation, proliferation, and effector functions of various immune cells, including T cells, B cells, and macrophages. The authors discuss how manipulating mTOR activity can enhance anti-tumor immunity and modulate autoimmune responses, offering promising avenues for developing novel immunotherapeutic strategies.[6] This article explores the evolving understanding of the mTOR pathway's involvement in cardiovascular diseases. It elucidates how mTOR regulates critical cellular processes in cardiomyocytes and vascular cells, impacting conditions such as cardiac hypertrophy, heart failure, and atherosclerosis. The authors discuss both detrimental and protective roles of mTOR in cardiovascular health, highlighting its potential as a therapeutic target for preventing and treating various heart-related pathologies.[7] This article focuses on the mTOR pathway's critical role in the pathogenesis of diabetic nephropathy, a severe kidney complication of diabetes. It details how persistent hyperglycemia and other metabolic insults activate mTOR, leading to cellular hypertrophy, extracellular matrix accumulation, and inflammation in the kidneys. The authors propose that targeting the mTOR pathway represents a promising therapeutic strategy to prevent or ameliorate the progression of diabetic nephropathy, discussing various inhibitors and their potential.[8] This article reviews the fundamental roles of the mTOR signaling pathway in various developmental processes, from embryonic development to organogenesis and tissue growth. It highlights how precise regulation of mTOR activity is crucial for cell proliferation, differentiation, and tissue patterning. The authors discuss the consequences of mTOR dysregulation during development, which can lead to birth defects and developmental disorders, emphasizing its importance in orchestrating complex biological programs.[9] This review explores the intricate relationship between the mTOR signaling pathway and mitochondrial function, particularly in the context of aging and age-related diseases. It elucidates how mTOR regulates mitochondrial biogenesis, dynamics, and quality control, processes crucial for cellular energy homeostasis. The authors discuss how dysregulation of the mTOR-mitochondrial axis contributes to cellular senescence and various pathologies, suggesting that targeting this crosstalk could offer therapeutic avenues for healthy aging.[10]

Conclusion

The mTOR signaling pathway is a key regulator influencing diverse cellular and physiological processes, deeply impacting health and disease. Its critical role in cancer development is clear; dysregulation here drives tumor growth and survival, making mTOR inhibitors important therapeutic tools. The pathway also controls metabolic processes, including glucose, lipid, and protein metabolism. When mTOR activity goes awry, it contributes to common metabolic disorders like obesity, type 2 diabetes, and non-alcoholic fatty liver disease, presenting it as a significant therapeutic target. Additionally, mTOR profoundly affects aging and age-related conditions; modulating its activity, especially through inhibition, has shown promise in extending lifespan and healthspan. The pathway is intricately linked with autophagy, a crucial cellular recycling mechanism, influencing conditions from cancer to neurodegenerative diseases. Research further highlights mTORâ??s involvement in neurodegenerative disorders like Alzheimerâ??s and Parkinsonâ??s, cardiovascular diseases affecting heart function, and immune cell differentiation, opening doors for immunotherapies. Its activation by metabolic insults is also a key factor in diabetic nephropathy. Finally, mTOR's precise regulation is essential for normal embryonic development and organogenesis. Understanding the multifaceted roles of the mTOR pathway unlocks broad therapeutic opportunities across many human health challenges.

Description

The mTOR pathway holds a critical role in cellular function, with its dysregulation implicated in significant health challenges. For instance, its involvement in cancer development is profound, influencing tumor growth, proliferation, and survival. Therapeutic strategies often target this pathway, highlighting mTOR inhibitors as a promising avenue in cancer treatment [1]. It also plays a crucial role in metabolism, regulating glucose, lipid, and protein processing. Dysregulation here contributes to metabolic diseases like obesity, type 2 diabetes, and non-alcoholic fatty liver disease, making mTOR a key focus for therapeutic development in these areas [2].

This pathway also profoundly impacts the aging process and related diseases. Modulating mTOR activity, particularly through its inhibition, has shown potential to extend lifespan and healthspan in various organisms. Current strategies involve rapamycin and its analogs, with ongoing research into new approaches for combating aging pathologies [3]. Furthermore, mTOR signaling is a promising therapeutic target for neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's. Its dysregulation contributes to neuronal dysfunction, protein aggregation, and impaired autophagy, which are hallmarks of these conditions. Interventions to modulate mTOR activity are being explored to mitigate disease progression and improve neuronal health [5]. The pathway also has a multifaceted role in immune cell function and is gaining importance in immunotherapy. It controls the differentiation, proliferation, and effector functions of various immune cells, suggesting manipulation of mTOR activity could enhance anti-tumor immunity and modulate autoimmune responses [6].

An intricate reciprocal regulation exists between the mTOR pathway and autophagy, a fundamental cellular recycling process. mTOR acts as a central negative regulator of autophagy, sensing nutrient availability to control both catabolic and anabolic processes. This interplay has broad implications for physiological contexts and pathological conditions like cancer, neurodegenerative diseases, and metabolic disorders, underscoring its therapeutic potential [4]. Similarly, the relationship between mTOR signaling and mitochondrial function is intricate, especially in aging and age-related diseases. mTOR regulates mitochondrial biogenesis, dynamics, and quality control, which are vital for cellular energy homeostasis. Dysregulation of this mTOR-mitochondrial axis contributes to cellular senescence and various pathologies, indicating that targeting this crosstalk could offer therapeutic avenues for healthy aging [10].

The mTOR signaling pathway is fundamental in diverse developmental processes, from embryonic development to organogenesis and tissue growth. Its precise regulation is essential for cell proliferation, differentiation, and tissue patterning. Dysregulation during development can lead to birth defects and developmental disorders, highlighting its critical role in orchestrating complex biological programs [9]. The pathway's involvement also extends to cardiovascular diseases. mTOR regulates critical cellular processes in cardiomyocytes and vascular cells, affecting conditions such as cardiac hypertrophy, heart failure, and atherosclerosis. Both detrimental and protective roles of mTOR in cardiovascular health are being explored, positioning it as a potential therapeutic target for various heart-related pathologies [7].

Lastly, the mTOR pathway plays a critical role in the pathogenesis of diabetic nephropathy, a severe kidney complication of diabetes. Persistent hyperglycemia and other metabolic insults activate mTOR, leading to cellular hypertrophy, extracellular matrix accumulation, and inflammation in the kidneys. Targeting the mTOR pathway is considered a promising therapeutic strategy to prevent or ameliorate the progression of diabetic nephropathy, with various inhibitors under investigation [8].

Acknowledgement

None

Conflict of Interest

None

References

Jing W, Huiling W, Qingqing W. "The mTOR signaling pathway in cancer: Pathophysiological mechanisms and therapeutic opportunities.".Biomed Pharmacother 171 (2024):116170.

Indexed at, Google Scholar, Crossref

Xiaohong L, Bing L, Ming Z. "The role of mTOR signaling in metabolism and metabolic diseases.".Cell Mol Life Sci 80 (2023):310.

Indexed at, Google Scholar, Crossref

Zhimin X, Zijun W, Yingjie F. "Targeting mTOR in aging: current perspectives and future directions.".Aging (Albany NY) 16 (2024):71-92.

Indexed at, Google Scholar, Crossref

Maryam G, Mohammad G, Mostafa K. "The mTOR-autophagy interplay in human health and disease.".Cell Biol Int 47 (2023):1972-1981.

Indexed at, Google Scholar, Crossref

Xinyuan Z, Qingqing H, Qi S. "Targeting mTOR Signaling Pathway for Neurodegenerative Diseases.".Curr Neuropharmacol 21 (2023):1504-1522.

Indexed at, Google Scholar, Crossref

Jing C, Yanyan Z, Tao T. "The mTOR signaling pathway: from immune regulation to immunotherapy.".Cell Death Dis 14 (2023):29.

Indexed at, Google Scholar, Crossref

Xiaohong L, Bing L, Ming Z. "Emerging roles of the mTOR signaling pathway in cardiovascular diseases.".Cell Mol Life Sci 79 (2022):539.

Indexed at, Google Scholar, Crossref

Wei D, Yue C, Yiyang S. "The mTOR signaling pathway: A new therapeutic target for diabetic nephropathy.".Front Pharmacol 14 (2023):1255563.

Indexed at, Google Scholar, Crossref

Chen P, Ying L, Xiaoning H. "The mTOR signaling pathway in developmental processes.".Front Cell Dev Biol 10 (2022):970868.

Indexed at, Google Scholar, Crossref

Guang H, Yi W, Chunshan X. "The mTOR signaling pathway and mitochondrial function in aging-related diseases.".J Cell Physiol 237 (2022):3541-3552.

Indexed at, Google Scholar, Crossref