Premium
Insulin inhibits Aβ fibrillogenesis through a decrease of the GM1 ganglioside‐rich microdomain in neuronal membranes
Author(s) -
Yamamoto Naoki,
Taniura Hideo,
Suzuki Kenji
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06620.x
Subject(s) - lipid microdomain , insulin , nerve growth factor , ganglioside , insulin receptor , medicine , endocrinology , amyloid (mycology) , microbiology and biotechnology , neurite , amyloid precursor protein , chemistry , biology , membrane , alzheimer's disease , biochemistry , receptor , insulin resistance , inorganic chemistry , disease , in vitro
J. Neurochem. (2010) 113 , 628–636. Abstract Type 2 diabetes is a risk factor for late‐onset Alzheimer’s disease. However, the underlying mechanisms remain unknown. To investigate whether insulin is associated with the assembly of amyloid β‐protein from the cell surface, we treated nerve growth factor (NGF)‐treated rat pheochromocytoma 12 (PC12) cells with insulin, which is related to the development of diabetes. Insulin treatment induced a decrease in GM1 ganglioside (GM1) levels in detergent‐resistant membrane microdomains of NGF‐treated PC12 cells. The insulin‐induced effects on GM1 levels were regulated by a phosphatidylinositol 3‐kinase inhibitor, but not by an extracellular signal‐regulated kinase inhibitor. Pre‐treatment with a protein synthesis inhibitor did not inhibit the decrease in GM1 levels induced by insulin. In addition, insulin failed to induce formation of fibrils from soluble amyloid β‐protein or to accelerate GM1‐induced fibril formation. Furthermore, assembly of amyloid β‐protein in cultures of NGF‐treated PC12 cells was significantly decreased by insulin. These results suggest that insulin inhibits amyloid β‐protein assembly by decreasing GM1 expression in detergent‐resistant membrane microdomains of neuronal membranes.