title: The Potential Role of Insulin on the Shank-Postsynaptic Platform in Neurodegenerative Diseases Involving Cognition.
abstract: Loss of synaptic function is critical in the pathogenesis of Alzheimer's disease (AD) and other central nervous system (CNS) degenerations. A promising candidate in the regulation of synaptic function is Shank, a protein that serves as a scaffold for excitatory synaptic receptors and proteins. Loss of Shank alters structure and function of the postsynaptic density (PSD). Shank proteins are associated with N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor loss at the PSD in AD; mutations in Shank also lead to autism spectrum disorders (ASDs) and schizophrenia, both of which affect cognition, suggesting that Shank may play a common pathologic role in AD, ASD, and schizophrenia. Shank protein directly associates with insulin receptor substrate protein p53 in PSD. Insulin and insulin sensitizers have been used in clinical trials for these diseases; this suggests that insulin signals may alter protein homeostasis at the shank-postsynaptic platform in PSDs; insulin could improve the function of synapses in these diseases.
authors.affiliation: Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Chow
authors.affiliation: Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA yuesong.gong@drexelmed.edu.
authors.forename: Yuesong
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Carol F
authors.initials: CF
authors.lastname: Lippa
mesh_terms: D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D057907:Post-Synaptic Density / Q000378:metabolism*
chemical_list: C119539:BAIAP2 protein, human; D007328:Insulin; D009419:Nerve Tissue Proteins; C574178:SHANK1 protein, human; C122162:SHANK2 protein, human; C492357:SHANK3 protein, human
keywords: Alzheimer’s disease; Shank; autism spectrum disorders; insulin; schizophrenia