| First Author | Barone E | Year | 2019 |
| Journal | Mol Neurobiol | Volume | 56 |
| Issue | 4 | Pages | 2922-2943 |
| PubMed ID | 30073505 | Mgi Jnum | J:311364 |
| Mgi Id | MGI:6759140 | Doi | 10.1007/s12035-018-1231-5 |
| Citation | Barone E, et al. (2019) Biliverdin Reductase-A Mediates the Beneficial Effects of Intranasal Insulin in Alzheimer Disease. Mol Neurobiol 56(4):2922-2943 |
| abstractText | 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 3xTg-AD mice by ameliorating BVR-A activation. These changes were associated with a reduction of nitrosative stress, Tau phosphorylation, and Abeta 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. |
