Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders: Ageing Research Reviews

C. Scassellati, A.C. Galoforo, C. Bonvicini, C. Esposito, G. Ricevuti

Research output: Contribution to journalArticlepeer-review


Systems medicine is founded on a mechanism-based approach and identifies in this way specific therapeutic targets. This approach has been applied for the transcription factor nuclear factor (erythroid-derived 2)–like 2 (Nrf2). Nrf2 plays a central role in different pathologies including neurodegenerative disorders (NDs), which are characterized by common pathogenetic features. We here present wide scientific background indicating how a natural bioactive molecule with antioxidant/anti-apoptotic and pro-autophagy properties such as the ozone (O3) can represent a potential new strategy to delay neurodegeneration. Our hypothesis is based on different evidence demonstrating the interaction between O3 and Nrf2 system. Through a meta-analytic approach, we found a significant modulation of O3 on endogenous antioxidant-Nrf2 (p < 0.00001, Odd Ratio (OR) = 1.71 95%CI:1.17-2.25) and vitagene-Nrf2 systems (p < 0.00001, OR = 1.80 95%CI:1.05-2.55). O3 activates also immune, anti-inflammatory signalling, proteasome, releases growth factors, improves blood circulation, and has antimicrobial activity, with potential effects on gut microbiota. Thus, we provide a consistent rationale to implement future clinical studies to apply the oxygen-ozone (O2-O3) therapy in an early phase of aging decline, when it is still possible to intervene before to potentially develop a more severe neurodegenerative pathology. We suggest that O3 along with other antioxidants (polyphenols, mushrooms) implicated in the same Nrf2-mechanisms, can show neurogenic potential, providing evidence as new preventive strategies in aging and in NDs. © 2020 The Author(s)
Original languageEnglish
Article number101138
JournalAgeing Res. Rev.
Publication statusPublished - 2020


  • antioxidant system
  • Neurodegenerative Disorders
  • nuclear factor (erythroid-derived 2)–like 2 (Nrf2)
  • Oxygen-Ozone (O2-O3) therapy
  • Ozone (O3)
  • stress oxidative biomarkers
  • biological marker
  • catalase
  • curcumin
  • flavonol derivative
  • Ginkgo biloba extract
  • glutathione
  • glutathione peroxidase
  • glutathione reductase
  • growth factor
  • mitochondrial permeability transition pore
  • oxygen
  • ozone
  • polyphenol derivative
  • proteasome
  • reactive nitrogen species
  • reactive oxygen metabolite
  • resveratrol
  • superoxide dismutase
  • transcription factor Nrf2
  • antioxidant
  • aged
  • aging
  • Alzheimer disease
  • amyotrophic lateral sclerosis
  • antiinflammatory activity
  • antimicrobial activity
  • antioxidant activity
  • apoptosis
  • autophagy (cellular)
  • biological activity
  • cell aging
  • cell death
  • circulation
  • confidence interval
  • degenerative disease
  • exercise
  • gene expression
  • human
  • Huntington chorea
  • intestine flora
  • lipid peroxidation
  • medicinal mushroom
  • mental deterioration
  • meta analysis (topic)
  • mitochondrion
  • nerve degeneration
  • nervous system development
  • neuroprotection
  • nonhuman
  • odds ratio
  • oxidation reduction state
  • oxidative stress
  • ozone therapy
  • Parkinson disease
  • protein secretion
  • Review
  • signal transduction
  • metabolism
  • Aging
  • Antioxidants
  • Humans
  • Neurodegenerative Diseases
  • NF-E2-Related Factor 2
  • Oxidative Stress
  • Ozone


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