ReviewInternational journal of molecular sciences2017
PERM Hypothesis: The Fundamental Machinery Able to Elucidate the Role of Xenobiotics and Hormesis in Cell Survival and Homeostasis.
Review in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 54 citations in OpenAlex.
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- Integrating Gut-Brain Axis: Exploring the Neurogastrointestinal Interactions and Therapeutic Potentials in Autism Spectrum Disorder.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Quantitative Treatments for Explaining the Mechanism and Kinetics of Catalytic Electron Transfers in Murburn Processes, Particularly Involving Heme Enzymes Like (Per)oxidases and P450s.BioMed research international · 2026Review
- The Neuroimmunology of Autism.Molecular neurobiology · 2025Review
- Murburn Bioenergetics and "Origins-Sustenance-Termination-Evolution of Life": Emergence of Intelligence from a Network of Molecules, Unbound Ions, Radicals and Radiations.International journal of molecular sciences · 2025Review
- Treadmill training protects valproic acid-induced autistic features via cerebellar AMPK/PPAR-γ dependent pathway and improves mitochondrial activity in mice.Scientific reports · 2025Article
- Review
- The Mito-Hormetic Mechanisms of Ozone in the Clearance of SARS-CoV2 and in the COVID-19 Therapy.Biomedicines · 2022Review
- Investigating the Neurotoxic Impacts of Arsenic and the Neuroprotective Effects of Dictyophora Polysaccharide Using SWATH-MS-Based Proteomics.Molecules (Basel, Switzerland) · 2022Article
- Targeting EDEM protects against ER stress and improves development and survival in C. elegans.PLoS genetics · 2022Article
- The biological activity of medical ozone in the hormetic range and the role of full expertise professionals.Frontiers in public health · 2022Article
- Insights on the mechanisms of action of ozone in the medical therapy against COVID-19.International immunopharmacology · 2021Review
- Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications.Biomedicines · 2021Review
- Oxidative Stress, Nutrition and Cancer: Friends or Foes?The world journal of men's health · 2021Review
- Protective Effect of Dictyophora Polysaccharides on Sodium Arsenite-Induced Hepatotoxicity: A Proteomics Study.Frontiers in pharmacology · 2021Article
- The Gut Microbiota and Oxidative Stress in Autism Spectrum Disorders (ASD).Oxidative medicine and cellular longevity · 2020Review
- Targeting Cancer with Phytochemicals via Their Fine Tuning of the Cell Survival Signaling Pathways.International journal of molecular sciences · 2018Review
- HTLV-1: A real pathogen or a runaway guest of a diseased cell?Journal of biosciences · 2018Review
- Regulation of the intestinal immune system by flavonoids and its utility in chronic inflammatory bowel disease.World journal of gastroenterology · 2018Review
- Is Mitochondria Biogenesis and Neuronal Loss Prevention in Rat Hippocampus Promoted by Apigenin?Basic and clinical neuroscienceArticle
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response. The "PERM hypothesis" suggests that xenobiotics can modulate this central signaling and the regulatory engine made fundamentally by the ER, mitochondria and proteasome, together with other ancillary components such as peroxisomes, by acting on the energetic balance, redox system and macromolecule turnover. In this context, reactive species and stressors are fundamentally signalling molecules that could act as negative-modulating signals if PERM-mediated control is offline, impaired or dysregulated, as occurs in metabolic syndrome, degenerative disorders, chronic inflammation and cancer. Calcium is an important oscillatory input of this regulation and, in this hypothesis, it might play a role in maintaining the correct rhythm of this PERM modulation, probably chaotic in its nature, and guiding cells to a more drastic decision, such as apoptosis. The commonest effort sustained by cells is to maintain their survival balance and the proterome has the fundamental task of supporting this mechanism. Mild stress is probably the main stimulus in this sense. Hormesis is therefore re-interpreted in the light of this hypothetical model and that experimental evidence arising from flavonoid and hormesis reasearch.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.