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Glycogen Synthase Kinase-3 as a Therapeutic Target for Cognitive Dysfunction in Neuropsychiatric Disorders

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Abstract

The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) is involved in a broad range of cellular processes including cell proliferation, apoptosis and inflammation. It is now also increasingly acknowledged as having a role to play in cognitive-related processes such as neurogenesis, synaptic plasticity and neural cell survival. Cognitive impairment represents a major debilitating feature of many neurodegenerative and psychiatric disorders, including Alzheimer’s disease, mood disorders, schizophrenia and fragile X syndrome, as well as being a result of traumatic brain injury or cranial irradiation. Accordingly, GSK-3 has been identified as an important therapeutic target for cognitive impairment, and recent preclinical studies have yielded important evidence demonstrating that GSK-3 inhibitors may be useful therapeutic interventions for restoring cognitive function in some of these brain disorders. The current review summarises the role of GSK-3 as a regulator of cognitive-dependent functions, examines current preclinical and clinical evidence of the potential of GSK-3 inhibitors as therapeutic agents for cognitive impairments in neuropsychiatric disorders, and offers some insight into the current obstacles that are impeding the clinical use of selective GSK-3 inhibitors in the treatment of cognitive impairment.

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Acknowledgments

Work in Olivia O’Leary’s and Yvonne Nolan’s laboratories is currently supported by a Grant from Science Foundation Ireland (12/IA/1537) and the University College Cork (UCC) Strategic Research Fund. No funding was specifically received for the preparation of this article. Olivia O’Leary and Yvonne Nolan declare that they have no conflict of interest.

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  1. Department of Anatomy and Neuroscience, Western Gateway Building, University College Cork, Room 4.10, Cork, Ireland

    Olivia O’Leary

  2. Department of Anatomy and Neuroscience, Western Gateway Building, University College Cork, Room 3.83, Cork, Ireland

    Yvonne Nolan

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O’Leary, O., Nolan, Y. Glycogen Synthase Kinase-3 as a Therapeutic Target for Cognitive Dysfunction in Neuropsychiatric Disorders. CNS Drugs 29, 1–15 (2015). https://doi.org/10.1007/s40263-014-0213-z

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