Fyn, a Potential Target for Alzheimer's Disease

Article type: Review Article

Authors: Yang, Kai^{a; 1} | Belrose, Jillian^{b; 1} | Trepanier, Catherine H.^c | Lei, Gang^d | Jackson, Michael F.^{d; e} | MacDonald, John F.^{a; b; c; d; e; *}

Affiliations: [a] Department of Physiology, University of Toronto, Toronto, ON, Canada | [b] Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada | [c] Department of Pharmacology and toxicology, University of Toronto, Toronto, ON, Canada | [d] Robarts Research Institute, Molecular Brain Research Group, University of Western Ontario, London, ON, Canada | [e] Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada

Correspondence: [*] Correspondence to: John F. MacDonald, Ph.D and Michael F. Jackson Ph.D, Robarts Research Institute, Molecular Brain Research Group, University of Western Ontario, 100 Perth Drive, London, ON N6A 5K8 Canada. Tel.: +1 (519) 931 5777, extension: 24240; Fax: +1 (519)931 5789; E-mail: jmacd53@uwo.ca (John F. MacDonald), mjacks32@uwo.ca (Michael F. Jackson).

Note: [1] These authors contributed equally to this work.

Abstract: Alzheimer's disease (AD) is the most common form of dementia characterized by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles. The mechanisms leading to AD are not completely understood; however, recent evidence suggests that alterations in Fyn, a Src family kinase, might contribute to AD pathogenesis. A number of studies have demonstrated that Fyn is involved in synaptic plasticity, a cellular mechanism for learning and memory. In addition, Fyn plays a role in the regulation of Aβ production and mediates Aβ-induced synaptic deficits and neurotoxicity. Fyn also induces tyrosine phosphorylation of tau. Although many studies have implicated a role for Fyn in AD, the precise cellular and molecular mechanisms require further investigation. Novel insights into the role of Fyn in AD may help identify alternative pharmacological approaches for the treatment of AD.

Keywords: Alzheimer's disease, AMPA receptors, amyloid-β, Fyn, NMDA receptors, synaptic plasticity, tau

DOI: 10.3233/JAD-2011-110353

Journal: Journal of Alzheimer's Disease, vol. 27, no. 2, pp. 243-252, 2011