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An isoform-specific role of FynT tyrosine kinase in Alzheimer's disease

Lookup NU author(s): Professor Johannes Attems

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Abstract

Alzheimer's disease (AD) is the leading cause of dementia in old age and is characterized by the accumulation of beta-amyloid plaques and neurofibrillary tangles (NFT). Recent studies suggest that Fyn tyrosine kinase forms part of a toxic triad with b-amyloid and tau in the disease process. However, it is not known whether Fyn is associated with the pathological features of AD in an isoform-specific manner. In this study, we identified selective up-regulation of the alternative-spliced FynT isoform with no change in FynB in the AD neocortex. Furthermore, gene ontology term enrichment analyses and cell type-specific localization of FynT immunoreactivity suggest that FynT up-regulation was associated with neurofibrillary degeneration and reactive astrogliosis. Interestingly, significantly increased FynT in NFT-bearing neurons was concomitant to decreased FynB immunoreactivity, suggesting an involvement of alternative splicing in NFT formation. Furthermore, cultured cells of astrocytic origin have higher FynT to FynB ratio compared to those of neuronal origin. Lastly, primary rat mixed neuron-astrocyte cultures treated with A beta(25-35) showed selective up-regulation of FynT expression in activated astrocytes. Our findings point to an isoform-specific role of FynT in modulating neurofibrillary degeneration and reactive astrogliosis in AD.

Publication metadata

Author(s): Lee C, Low CYB, Francis PT, Attems J, Wong PTH, Lai MKP, Tan MGK

Publication type: Article

Publication status: Published

Journal: Journal of Neurochemistry

Year: 2016

Volume: 136

Issue: 3

Pages: 637-650

Print publication date: 01/02/2016

Online publication date: 19/01/2016

Acceptance date: 06/11/2015

ISSN (print): 0022-3042

ISSN (electronic): 1471-4159

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/jnc.13429

DOI: 10.1111/jnc.13429

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