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Am J Alzheimers Dis Other Demen. 2014 Jun;29(4):303-10. doi: 10.1177/1533317513518645. Epub 2014 Jan 13.

The Potential Role of Insulin on the Shank-Postsynaptic Platform in Neurodegenerative Diseases Involving Cognition.

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Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA.
Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA


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.


Alzheimer’s disease; Shank; autism spectrum disorders; insulin; schizophrenia

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