Inhalation exposure-induced toxicity and disease mediated via mTOR dysregulation

Exp Biol Med (Maywood). 2024 Apr 22:249:10135. doi: 10.3389/ebm.2024.10135. eCollection 2024.

Abstract

Environmental air pollution is a global health concern, associated with multiple respiratory and systemic diseases. Epidemiological supports continued urbanization and industrialization increasing the prevalence of inhalation exposures. Exposure to these inhaled pollutants induces toxicity via activation of numerous cellular mechanisms including oxidative stress, autophagy, disrupted cellular metabolism, inflammation, tumorigenesis, and others contributing to disease development. The mechanistic target of rapamycin (mTOR) is a key regulator involved in various cellular processes related to the modulation of metabolism and maintenance of homeostasis. Dysregulation of mTOR occurs following inhalation exposures and has also been implicated in many diseases such as cancer, obesity, cardiovascular disease, diabetes, asthma, and neurodegeneration. Moreover, mTOR plays a fundamental role in protein transcription and translation involved in many inflammatory and autoimmune diseases. It is necessary to understand inhalation exposure-induced dysregulation of mTOR since it is key regulator which may contribute to numerous disease processes. This mini review evaluates the available literature regarding several types of inhalation exposure and their impacts on mTOR signaling. Particularly we focus on the mTOR signaling pathway related outcomes of autophagy, lipid metabolism, and inflammation. Furthermore, we will examine the implications of dysregulated mTOR pathway in exposure-induced diseases. Throughout this mini review, current gaps will be identified related to exposure-induced mTOR dysregulation which may enable the targeting of mTOR signaling for the development of therapeutics.

Keywords: autophagy; inflammation; inhalation toxicology; lipid homeostasis; lung disease; mTOR; metabolism.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Humans
  • Inflammation / metabolism
  • Inhalation Exposure* / adverse effects
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • TOR Serine-Threonine Kinases
  • MTOR protein, human

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by the National Institute of Environmental Health Sciences (NIEHS) Grant R01ES033173.