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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 263673, 8 pages
Review Article

The Role of GSK3 in Presynaptic Function

Membrane Biology Group, Centre for Integrative Physiology, University of Edinburgh, George Square, EH8 9XD, Edinburgh, UK

Received 30 November 2010; Accepted 20 January 2011

Academic Editor: Peter Crouch

Copyright © 2011 Karen Janet Smillie and Michael Alan Cousin. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The past ten years of research have identified a number of key roles for glycogen synthase kinase 3 (GSK3) at the synapse. In terms of presynaptic physiology, critical roles for GSK3 have been revealed in the growth and maturation of the nerve terminal and more recently a key role in the control of activity-dependent bulk endocytosis of synaptic vesicles. This paper will summarise the major roles assigned to GSK3 in both immature and mature nerve terminals, the substrates GSK3 phosphorylates to exert its action, and how GSK3 activity is regulated by different presynaptic signalling cascades. The number of essential roles for GSK3, coupled with the numerous signalling cascades all converging to regulate its activity, suggests that GSK3 is a key integrator of multiple inputs to modulate the strength of neurotransmission. Modulation of these pathways may point to potential mechanisms to overcome synaptic failure in neurodegenerative disorders such as Alzheimer's disease.