Enhanced neprilysin-mediated degradation of hippocampal Aβ42 with a somatostatin peptide that enters the brain
Fadi Rofo, Canan Uğur Yılmaz, Nicole G. Metzendorf, Tobias Gustavsson, Chiara Beretta, Anna Erlandsson, Dag Sehlin, Stina Syvänen, Per Nilsson, Greta Hultqvist
Abstract
With intravenous injections of our BBB permeable SST peptide, we were able to significantly increase the levels neprilysin, an effect that was followed by a significant and selective degradation of membrane-bound Aβ42 in the hippocampus. Being that membrane-bound Aβ triggers neuronal toxicity and the hippocampus is the central brain area in the progression of AD, the study has illuminated a new potential treatment paradigm with a promising safety profile targeting only the disease affected areas.
Topics & Concepts
NeprilysinSomatostatinChemistryNeuropeptideEndocrinologyInternal medicineHippocampusBlood–brain barrierHippocampal formationReceptorEnzymeBiologyBiochemistryCentral nervous systemMedicineAlzheimer's disease research and treatmentsNeuropeptides and Animal PhysiologyGenetics and Neurodevelopmental Disorders