[Improving Effects of Peptides on Brain Malfunction and Intranasal Delivery of Those Derivatives to the Brain].

[Improving Effects of Peptides on Brain Malfunction and Intranasal Delivery of Those Derivatives to the Brain]. Yakugaku Zasshi. 2019;139(5):783-791 Authors: Oka JI Abstract This review focuses on the anti-dementia and antidepressant-like effects of peptides including glucagon-like peptide (GLP)-1, GLP-2, neuromedin U (NmU), and oxytocin, and the intranasal delivery of these peptides to the brain. Intracerebroventricularly administered GLP-1, NmU, and oxytocin improved impairment of learning and memory in mice treated with lipopolysaccharide or β-amyloid protein. GLP-1 also improved impairment of learning and memory in juvenile diabetes model rats. On the other hand, GLP-2 exhibited antidepressant-like effects in mice during the forced-swim test, which were associated with 5-HT1A, α2, β1, and D2 receptors. GLP-2 also exerted antidepressant-like effects in adrenocorticotropic hormone (ACTH)-treated mice through restoration of the hypothalamic-pituitary-adrenal-axis and neurogenesis in the subgranular zone of the dentate gyrus. Because intracerebroventricular administration is invasive and the peptides are unable to penetrate the blood-brain barrier, we introduced our new method of intranasal administration to deliver the peptides to the brain. We prepared a GLP-2 derivative containing cell-penetrating peptides (CPPs) and a penetration accelerating sequence (PAS). Intranasally administered PAS-CPPs-GLP-2 was distributed throughout t...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research