Interdisciplinary Program in Neuroscience, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Acta Neuropathol Commun. 2020 Jul 14;8(1):108. doi: 10.1186/s40478-020-00979-6.
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 tau 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, tau-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.
Src 家族非受体酪氨酸激酶 Fyn 通过与淀粉样蛋白 β（Aβ）相互作用，被认为与阿尔茨海默病的神经退行性变有关。然而，Fyn 在原发性 tau 病（如 FTDP-17）发病机制中的作用，在这些疾病中不存在 Aβ 斑块，目前了解甚少。在本研究中，我们使用 AAV2/8 载体将 tau 递送到 WT 和 Fyn KO 小鼠的大脑中，生成存在或不存在 Fyn 的体细胞转基因 tau 病模型。尽管两种基因型都发展出 tau 病理学，但 Fyn KO 在 Bielschowsky 和 Thioflavin S 染色切片上的神经纤维缠结较少，磷酸化 tau 水平较低。此外，在 Fyn KO 模型中未观察到 tau 诱导的行为异常和突触蛋白耗竭。我们的工作为 Fyn 是 FTDP-17 发病机制中的关键蛋白提供了证据。
