Biliverdin reductase-A mediates the beneficial effects of intranasal insulin in Alzheimer disease.

Eugenio Barone, Antonella Tramutola, Francesca Triani, Silvio Calcagnini, Fabio Di Domenico, Cristian Ripoli, Silvana Gaetani, Claudio Grassi, D Allan Butterfield, Tommaso Cassano, Marzia Perluigi

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37 Citazioni (Scopus)


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.
Lingua originaleEnglish
pagine (da-a)2922-2943
Numero di pagine22
RivistaMolecular Neurobiology
Stato di pubblicazionePubblicato - 2019


  • Alzheimer disease
  • Biliverdin reductase-A
  • Insulin resistance
  • Intranasal
  • Neuroprotection


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