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Updated: Jan 25, 2026
A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction
Published on: August 27, 2019
Mammalian Target of Rapamycin: Is It Relevant to COPD Pathogenesis or Treatment?
Evasio Pasini1, Vincenzo Flati2, Laura Comini3
1a Cardiac Rehabilitation of the Institute of Lumezzane , Istituti Clinici Scientifici Maugeri IRCCS , Brescia , Italy.
Abstract:
The mammalian target of rapamycin (mTOR) signalling pathway regulates fundamental metabolic processes such as inflammation, autophagy and apoptosis, all of which influence cell fate. Recent experimental data suggest that mTOR signalling is involved in many diseases, including lung diseases, but with contrasting data. Overexpression of mTOR and its signalling proteins have been linked to lung cell senescence and development of emphysema, pulmonary hypertension and inflammation. On the other hand, mTOR inhibitors, as rapamycin and/or its derivatives, restore corticosteroid sensitivity in peripheral blood mononuclear cells from chronic obstructive pulmonary disease (COPD) patients, and overexpression of mTOR suppresses cigarette smoke-induced inflammation and emphysema, suggesting that induction of mTOR expression/activity might be useful to treat COPD. This apparent discrepancy is due to complex and heterogenic enzymatic pathway of mTOR. Translation of pre-clinical positive data on the use of mTOR inhibitors to COPD therapy needs a more in-depth knowledge of mTOR signalling.
Insights
The mammalian target of rapamycin (mTOR) pathway impacts lung diseases like COPD. Understanding its complex role is key to developing new mTOR inhibitor therapies for lung conditions.
Area of Science:
- Cellular Biology
- Molecular Biology
- Pulmonary Medicine
Background:
- The mammalian target of rapamycin (mTOR) pathway is crucial for cellular metabolism, influencing inflammation, autophagy, and apoptosis.
- mTOR signalling is implicated in various lung diseases, but existing data present conflicting findings regarding its role and therapeutic potential.
- Overexpression of mTOR has been associated with lung diseases such as emphysema and pulmonary hypertension, while mTOR inhibitors show promise in treating chronic obstructive pulmonary disease (COPD).
Purpose of the Study:
- To investigate the complex and heterogeneous role of the mammalian target of rapamycin (mTOR) signalling pathway in lung diseases.
- To reconcile conflicting experimental data regarding mTOR's involvement in conditions like COPD.
- To highlight the need for a deeper understanding of mTOR signalling for the translation of preclinical findings into effective COPD therapies.
Main Methods:
- Review of recent experimental data and literature on mTOR signalling in lung diseases.
- Analysis of studies investigating mTOR overexpression and the effects of mTOR inhibitors (e.g., rapamycin) in models of lung disease and COPD.
- Examination of the complex enzymatic pathways associated with mTOR.
Main Results:
- Conflicting evidence exists regarding mTOR's role in lung diseases; overexpression is linked to emphysema and pulmonary hypertension.
- mTOR inhibitors can restore corticosteroid sensitivity in COPD patients' cells.
- mTOR overexpression appears to suppress inflammation and emphysema induced by cigarette smoke, suggesting a potential therapeutic benefit.
Conclusions:
- The mammalian target of rapamycin (mTOR) pathway has a complex and context-dependent role in lung diseases, including COPD.
- The apparent discrepancies in mTOR's function are attributed to its intricate and heterogeneous signalling.
- Further in-depth research into mTOR signalling mechanisms is essential for the successful clinical application of mTOR inhibitors in COPD treatment.
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