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The expression of NLRP3-inflammasome, phospho-Tau181, glycogen synthase kinase-3 beta (GSK-3\u03b2), cyclin-dependent kinase 5 (CdK5), and histone deacetylase 6 (HDAC6), was quantified by flow cytometry. Drug distribution in the mice's brains was assessed by liquid chromatography-mass spectrometry (LC-MS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      significantly reduced cell viability and increased apoptosis, which was reversed by using gliflozins. SGLT2i significantly reduced A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      -induced reactive oxygen species generation, downregulated NLRP3-inflammasome, and diminished tau pathology. Mechanistically, the last effect involved the modulation of GSK-3\u03b2 and CdK5 protein expression. However, the tested treatments did not modify the A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      -stimulating effect of HDAC6. Gliflozins are substrates of drug transporters ATP-binding cassette sub-family B member 1 and\/or ATP binding cassette subfamily G member 2 (ABCB1 and ABCG2), and Elacridar significantly enhances their brain distribution.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SGLT2i empagliflozin and dapagliflozin exhibited neuroprotective actions against human A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      -induced neurotoxicity.\n                    <\/jats:p>\n                  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