Biliverdin Reductase-A Mediates the Beneficial Effects of Intranasal Insulin in Alzheimer Disease
Autor
Barone E.
Tramutola A.
Triani F.
Calcagnini S.
Di Domenico F.
Ripoli C.
Gaetani S.
Grassi C.
Butterfield D.A.
Cassano T.
Perluigi M.
Resumen
Impairment of biliverdin reductase-A (BVR-A) is an early event leading to brain insulin resistance in AD. Intranasal insulin (INI) administration is under evaluation as a strategy to alleviate brain insulin resistance; however, the molecular mechanisms underlying INI beneficial effects are still unclear. We show that INI improves insulin signaling activation in the hippocampus and cortex of adult and aged 3×Tg-AD mice by ameliorating BVR-A activation. These changes were associated with a reduction of nitrosative stress, Tau phosphorylation, and Aβ oligomers in brain, along with improved cognitive functions. The role of BVR-A was strengthened by showing that cells lacking BVR-A: (i) develop insulin resistance if treated with insulin and (ii) can be recovered from insulin resistance only if treated with a BVR-A-mimetic peptide. These novel findings shed light on the mechanisms underlying INI treatment effects and suggest BVR-A as potential therapeutic target to prevent brain insulin resistance in AD. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Colecciones
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Article
Impairment of biliverdin reductase-A promotes brain insulin resistance in Alzheimer disease: A new paradigm (2020)
Barone E.; Di Domenico F.; Cassano T.; Arena A.; Tramutola A.; Lavecchia M.A.; Coccia R.; Butterfield D.A.; Perluigi M. (Elsevier Inc., 2016) -
Article
Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways (2020)
Ettcheto M.; Sánchez-López E.; Pons L.; Busquets O.; Olloquequi J.; Beas-Zarate C.; Pallas M.; García M.L.; Auladell C.; Folch J.; ... (Elsevier B.V., 2017) -
Article
Proteomic identification of altered protein O-GlcNAcylation in a triple transgenic mouse model of Alzheimer's disease (2020)
Tramutola A.; Sharma N.; Barone E.; Lanzillotta C.; Castellani A.; Iavarone F.; Vincenzoni F.; Castagnola M.; Butterfield D.A.; Gaetani S.; ... (Elsevier B.V., 2018)