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Nygaard HB, van Dyck CH, Strittmatter SM. Fyn kinase inhibition as a novel therapy for Alzheimer's disease. Alzheimers Res Ther. 2014;6(1):8doi: 10.1186/alzrt238.
Nygaard, H. B., van Dyck, C. H., & Strittmatter, S. M. (2014). Fyn kinase inhibition as a novel therapy for Alzheimer's disease. Alzheimer's research & therapy, 6(1), 8. https://doi.org/10.1186/alzrt238
Nygaard, Haakon B, et al. "Fyn kinase inhibition as a novel therapy for Alzheimer's disease." Alzheimer's research & therapy vol. 6,1 (2014): 8. doi: https://doi.org/10.1186/alzrt238
Nygaard HB, van Dyck CH, Strittmatter SM. Fyn kinase inhibition as a novel therapy for Alzheimer's disease. Alzheimers Res Ther. 2014 Feb 05;6(1):8. doi: 10.1186/alzrt238. eCollection 2014. PMID: 24495408; PMCID: PMC3978417.
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Alzheimers Res Ther. 2014 Feb 05;6(1):8. doi: 10.1186/alzrt238. eCollection 2014.

Fyn kinase inhibition as a novel therapy for Alzheimer's disease.

Alzheimer's research & therapy

Haakon B Nygaard, Christopher H van Dyck, Stephen M Strittmatter

Affiliations

  1. Department of Neurology, Yale University School of Medicine, PO Box 208018, New Haven, CT 06520, USA ; Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, 295 Congress Avenue, BCMM 436, New Haven, CT 06536, USA.
  2. Alzheimer's Disease Research Unit, Yale University School of Medicine, 1 Church Street, Suite 600, New Haven, CT 06510, USA ; Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT 06511, USA.

PMID: 24495408 PMCID: PMC3978417 DOI: 10.1186/alzrt238

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder, afflicting more than one-third of people over the age of 85. While many therapies for AD are in late-stage clinical testing, rational drug design based on distinct signaling pathways in this disorder is only now emerging. Here we review the putative signaling pathway of amyloid-beta (Aβ), by which the tyrosine kinase Fyn is activated via cell surface binding of Aβ oligomers to cellular prion protein. Several lines of evidence implicate Fyn in the pathogenesis of AD, and its interaction with both Aβ and Tau renders Fyn a unique therapeutic target that addresses both of the major pathologic hallmarks of AD. We are currently enrolling patients in a phase Ib study of saracatinib (AZD0530), a small molecule inhibitor with high potency for Src and Fyn, for the treatment of AD. The results of this trial and a planned phase IIa multisite study will provide important data regarding the potential for this therapeutic strategy in AD.

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