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GLUT inhibitor WZB117 induces cytotoxicity with increased production of amyloid-beta peptide in SH-SY5Y cells preventable by beta-hydroxybutyrate: implications in Alzheimer�s disease

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dc.contributor.authorChandan, Gourav
dc.contributor.authorGanguly, Upasana
dc.contributor.authorPal, Soumya
dc.contributor.authorSingh, Sukhpal
dc.contributor.authorSaini, Reena V.
dc.contributor.authorChakrabarti, Sankha Shubhra
dc.contributor.authorSaini, Adesh K.
dc.contributor.authorChakrabarti, Sasanka
dc.date.accessioned2025-01-28T09:49:45Z
dc.date.available2025-01-28T09:49:45Z
dc.date.issued2023
dc.description.abstractBackground: Inhibitors of glucose transporters are being explored as potential anti-cancer drugs. Decreased cerebral glucose utilization with reduced levels of several glucose transporters is also an important pathogenic signature of neurodegeneration of Alzheimer�s disease, but its exact role in the pathogenesis of this disease is not established. We explored in an experimental model if inhibitors of glucose transporters could lead to altered amyloid-beta homeostasis, mitochondrial dysfunction, and neuronal death, which are relevant in the pathogenesis of Alzheimer�s disease. Methods: SH-SY5Y cells (human neuroblastoma cell line) were exposed to an inhibitor (WZB117) of several types of glucose transporters. We examined the effects of glucose hypometabolism on SH-SY5Y cells in terms of mitochondrial functions, production of reactive oxygen species, amyloid-beta homeostasis, and neural cell death. The effect of ?-hydroxybutyrate in ameliorating the effects of WZB117 on SH-SY5Y cells was also examined. Results: We observed that exposure of SH-SY5Y cells to WZB117 caused mitochondrial dysfunction, increased production of reactive oxygen species, loss of cell viability, increased expression of BACE 1, and intracellular accumulation of amyloid ? peptide (A?42). All the effects of WZB117 could be markedly prevented by co-treatment with ?-hydroxybutyrate. Cyclosporine A, a blocker of mitochondrial permeability transition pore (mPTP) activation, could not prevent cell death caused by WZB117. Conclusion: Results in this neuroblastoma model have implications for the pathogenesis of Alzheimer�s disease and warrant further explorations of WZB117 in primary cultures of neurons and experimental animal models. � 2023, The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.
dc.identifier.doihttps://doi.org/10.1007/s43440-023-00466-4
dc.identifier.issn17341140
dc.identifier.urihttps://dl.bhu.ac.in/ir/handle/123456789/22521
dc.language.isoen
dc.publisherSpringer Science and Business Media Deutschland GmbH
dc.subjectAmyloid beta peptide
dc.subjectGlucose transporter
dc.subjectMitochondria
dc.subjectNeurodegeneration
dc.subjectReactive oxygen species
dc.titleGLUT inhibitor WZB117 induces cytotoxicity with increased production of amyloid-beta peptide in SH-SY5Y cells preventable by beta-hydroxybutyrate: implications in Alzheimer�s disease
dc.typeArticle
dspace.entity.typePublication
journal.titlePharmacological Reports
journalvolume.identifier.volume75

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2023