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To cope with the elevated oxidative stress they generate, cancer cells enhance their antioxidant capacity, largely through sustained activation of the transcription factor NRF2 often driven by mutations in its negative regulator KEAP1

261 On the other hand, SIRT4 suppresses tumor growth by inhibiting glutamine metabolism, 262,263 and upon downregulation, it inhibits apoptosis and desensitizes cancer cells to chemotherapy

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A literature search was conducted from January 2000 to December 2022 using multiple databases including Web of Science, Wiley, Springer, PubMed, Elsevier Science Direct, Google Scholar, the Core Collection, Scopus, and the Cochrane Library to collect and evaluate peer-reviewed literature regarding the neuroprotective role of metformin against DM-induced neurodegenerative events

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