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7459390 
Journal Article 
Review 
Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders 
Scassellati, C; Galoforo, AC; Bonvicini, C; Esposito, C; Ricevuti, G 
2020 
Yes 
Ageing Research Reviews
ISSN: 1568-1637 
Elsevier Ireland Ltd 
63 
101138 
English 
32810649 
WOS:000575075600003 
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) 
antioxidant system; Neurodegenerative Disorders; nuclear factor (erythroid-derived 2)–like 2 (Nrf2); Oxygen-Ozone (O2-O3) therapy; Ozone (O3); stress oxidative biomarkers