Insulin Signaling Differentially Regulates the Trafficking of Insulin and Amyloid Beta Peptides at the Blood–Brain Barrier

• DOI: 10.1021/acs.molpharmaceut.3c00784
• Publication Date: 2024-04-16T14:11:29Z
• Authors: Andrew L. Zhou; Suresh K. Swamina...; Vrishali S. Salian; Lushan Wang; Geoffry L. Curran; Hoon-Ki Min; Val J. Lowe; Karunya K. Kandim...
• Keywords: Male; Amyloid beta-Peptides; Single Photon Emission Computed Tomography Computed Tomography; Brain; Tyrphostins; Receptor, Insulin; Peptide Fragments; Receptor, IGF Type 1; Mice, Inbred C57BL; Iodine Radioisotopes; Mice; Blood-Brain Barrier; Alzheimer Disease; Animals; Insulin; Signal Transduction

The blood-brain barrier (BBB) is instrumental in clearing toxic metabolites from the brain, such as amyloid-β (Aβ) peptides, and delivering essential nutrients to like insulin. In Alzheimer's disease (AD) increased Aβ levels are paralleled by decreased insulin levels, which accompanied signaling deficits at BBB. Thus, we investigated impact of insulin-like growth factor receptor (IGF1R IR) on trafficking Following intravenous infusion an IGF1R/IR kinase inhibitor (AG1024) wild-type mice, BBB