Fyn depletion ameliorates tauP301L-induced neuropathology

Guanghao Liu; Kimberly L Fiock; Yona Levites; Todd E Golde; Marco M Hefti; Gloria Lee

doi:10.1186/s40478-020-00979-6

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Fyn depletion ameliorates tauP301L-induced neuropathology

Journal article

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Peer reviewed

Fyn depletion ameliorates tauP301L-induced neuropathology

Guanghao Liu, Kimberly L Fiock, Yona Levites, Todd E Golde, Marco M Hefti and Gloria Lee

Acta neuropathologica communications, Vol.8(1), pp.1-108

07/14/2020

DOI: 10.1186/s40478-020-00979-6

PMCID: PMC7362472

PMID: 32665013

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Abstract

The Src family non-receptor tyrosine kinase Fyn has been implicated in neurodegeneration of Alzheimer’s disease through interaction with amyloid β (Aβ). However, the role of Fyn in the pathogenesis of primary tauopathies such as FTDP-17, where Aβ plaques are absent, is poorly understood. In the current study, we used AAV2/8 vectors to deliver tauP301L to the brains of WT and Fyn KO mice, generating somatic transgenic tauopathy models with the presence or absence of Fyn. Although both genotypes developed tau pathology, Fyn KO developed fewer neurofibrillary tangles on Bielschowsky and Thioflavin S stained sections and showed lower levels of phosphorylated tau. In addition, tauP301L-induced behavior abnormalities and depletion of synaptic proteins were not observed in the Fyn KO model. Our work provides evidence for Fyn being a critical protein in the disease pathogenesis of FTDP-17.

Details

Title: Subtitle: Fyn depletion ameliorates tauP301L-induced neuropathology
Creators: Guanghao Liu
Kimberly L Fiock
Yona Levites
Todd E Golde
Marco M Hefti
Gloria Lee
Resource Type: Journal article
Publication Details: Acta neuropathologica communications, Vol.8(1), pp.1-108
DOI: 10.1186/s40478-020-00979-6
PMID: 32665013
PMCID: PMC7362472
NLM abbreviation: Acta Neuropathol Commun
ISSN: 2051-5960
eISSN: 2051-5960
Grant note: DOI: 10.13039/100000049, name: National Institute on Aging, award: R01 AG017753, F30 AG054134; DOI: 10.13039/100000957, name: Alzheimer's Association, award: IIRG-12-241042; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: K23 NS109284
Language: English
Date published: 07/14/2020
Academic Unit: Pathology; Iowa Neuroscience Institute; Immunology; Internal Medicine
Record Identifier: 9984070157202771

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