Fyn kinase: a key mechanistic regulator and therapeutic target in tauopathy and neurodegenerative diseases.

Authors

Haiwen Wang, Xing Fan, Jianchao Ping, Qian Shao, Cai Wang, Hao Wang, Qiuhong Ji, Min Su, Wei Qian

Published in

Translational neurodegeneration. Volume 15. Issue 1. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

Synaptic dysfunction and intracellular accumulation of pathological tau are convergent hallmarks of Alzheimer's disease (AD) and related tauopathies, yet the molecular mechanisms coupling these events to widespread neurodegeneration remain incompletely understood. The Src family kinase Fyn has emerged as a critical signaling hub that integrates upstream pathogenic triggers, such as amyloid-β (Aβ), with downstream neurotoxic cascades. Here, we review the multifaceted roles of Fyn in orchestrating synaptic failure, highlighting how Fyn recruitment by mislocalized tau promotes N-methyl-D-aspartate receptor hyperactivation and calcium dysregulation. We examine the biophysical basis of Fyn-tau interactions, particularly the role of liquid-liquid phase separation in stabilizing toxic signaling complexes. We also discuss how aberrant Fyn signaling in microglia and astrocytes amplifies neuroinflammation. Finally, we evaluate the potential of Fyn as a therapeutic target, emphasizing the necessity of strategies that selectively uncouple pathological signaling from physiological functions to effectively halt disease progression.

PMID:
42816892
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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