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Biliverdin Reductase-A Mediates the Beneficial Effects of Intranasal Insulin in Alzheimer Disease
dc.contributor.author | Barone E. | |
dc.contributor.author | Tramutola A. | |
dc.contributor.author | Triani F. | |
dc.contributor.author | Calcagnini S. | |
dc.contributor.author | Di Domenico F. | |
dc.contributor.author | Ripoli C. | |
dc.contributor.author | Gaetani S. | |
dc.contributor.author | Grassi C. | |
dc.contributor.author | Butterfield D.A. | |
dc.contributor.author | Cassano T. | |
dc.contributor.author | Perluigi M. | |
dc.date.accessioned | 2020-09-02T22:12:59Z | |
dc.date.available | 2020-09-02T22:12:59Z | |
dc.date.issued | 2019 | |
dc.identifier | 10.1007/s12035-018-1231-5 | |
dc.identifier.citation | 56, 4, 2922-2943 | |
dc.identifier.issn | 08937648 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12728/3684 | |
dc.description | 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. | |
dc.language.iso | en | |
dc.publisher | Humana Press Inc. | |
dc.subject | Alzheimer disease | |
dc.subject | Biliverdin reductase-A | |
dc.subject | Insulin resistance | |
dc.subject | Intranasal | |
dc.subject | Neuroprotection | |
dc.subject | amyloid beta protein | |
dc.subject | biliverdin reductase A | |
dc.subject | human insulin | |
dc.subject | insulin receptor substrate 1 | |
dc.subject | oxidoreductase | |
dc.subject | tau protein | |
dc.subject | unclassified drug | |
dc.subject | biliverdin reductase | |
dc.subject | biological marker | |
dc.subject | insulin | |
dc.subject | insulin receptor substrate | |
dc.subject | Irs1 protein, mouse | |
dc.subject | oxidoreductase | |
dc.subject | adult | |
dc.subject | aged | |
dc.subject | Alzheimer disease | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | Article | |
dc.subject | controlled study | |
dc.subject | depression | |
dc.subject | frontal cortex | |
dc.subject | hippocampal CA1 region | |
dc.subject | hippocampal CA3 region | |
dc.subject | hippocampus | |
dc.subject | insulin resistance | |
dc.subject | insulin signaling | |
dc.subject | long term memory | |
dc.subject | long term potentiation | |
dc.subject | male | |
dc.subject | mouse | |
dc.subject | neuroprotection | |
dc.subject | nitrosative stress | |
dc.subject | nonhuman | |
dc.subject | oxidative stress | |
dc.subject | protein phosphorylation | |
dc.subject | short term memory | |
dc.subject | spatial learning | |
dc.subject | spatial memory | |
dc.subject | aging | |
dc.subject | Alzheimer disease | |
dc.subject | animal | |
dc.subject | animal behavior | |
dc.subject | cell line | |
dc.subject | complication | |
dc.subject | depression | |
dc.subject | drug effect | |
dc.subject | enzymology | |
dc.subject | intranasal drug administration | |
dc.subject | memory | |
dc.subject | memory disorder | |
dc.subject | metabolism | |
dc.subject | pathology | |
dc.subject | pathophysiology | |
dc.subject | phenotype | |
dc.subject | signal transduction | |
dc.subject | transgenic mouse | |
dc.subject | Administration, Intranasal | |
dc.subject | Aging | |
dc.subject | Alzheimer Disease | |
dc.subject | Animals | |
dc.subject | Behavior, Animal | |
dc.subject | Biomarkers | |
dc.subject | Cell Line | |
dc.subject | Depression | |
dc.subject | Hippocampus | |
dc.subject | Insulin | |
dc.subject | Insulin Receptor Substrate Proteins | |
dc.subject | Insulin Resistance | |
dc.subject | Long-Term Potentiation | |
dc.subject | Male | |
dc.subject | Memory | |
dc.subject | Memory Disorders | |
dc.subject | Mice, Transgenic | |
dc.subject | Oxidative Stress | |
dc.subject | Oxidoreductases Acting on CH-CH Group Donors | |
dc.subject | Phenotype | |
dc.subject | Signal Transduction | |
dc.title | Biliverdin Reductase-A Mediates the Beneficial Effects of Intranasal Insulin in Alzheimer Disease | |
dc.type | Article |