Role of Fyn Kinase Inhibitors in Switching Neuroinflammatory Pathways

Abstract

Fyn kinase is a member of the Src non-receptor tyrosine kinase family. Fyn is involved in multiple signaling pathways extending from cell proliferation and differentiation to cell adhesion and cell motility, and it has been found to be overexpressed in various types of cancers. In the central nervous system, Fyn exerts several different functions such as axon–glial signal transduction, oligodendrocyte maturation and myelination, and it is implicated in neuroinflammatory processes. Based on these premises, Fyn emerges as an attractive target in cancer and neurodegenerative disease therapy, particularly Alzheimer disease (AD), based on its activation by Aβ via cellular prion protein and its interaction with tau protein. However, Fyn is also a challenging target since the Fyn inhibitors discovered so far, due to the relevant homology of Fyn with other kinases, suffer from off-target effects. This review covers the efforts performed in the last decade to identify and optimize small molecules that effectively inhibit Fyn, both in enzymatic and in cell assays, including drug repositioning practices, as an opportunity of therapeutic intervention in neurodegeneration.

Circ‐POSTN promotes the progression and reduces radiosensitivity in esophageal cancer by regulating the miR‐876‐5p/FYN axis

“…We confirmed that FYN was targeted by miR‐876‐5p. FYN plays an essential role in diverse cellular processes 28,29 . In addition, previous studies showed that FYN served as a tumor accelerator in multiple cancers 17,30,31 .…”

Expression profiling of mRNA and functional network analyses of genes regulated by human papilloma virus E6 and E7 proteins in HaCaT cells

“…The expression of E6 and E7 resulted in the detection of many DEGs using RNA-seq and RT-qPCR. Fourteen of these hub genes were linked to cell adhesion ( Chute, 2006 ; Teicher and Fricker, 2010 ; Paolillo and Schinelli, 2019 ; Marotta et al, 2021 ), leukocyte–endothelial migration ( Yakovlev et al, 2019 ; Morein et al, 2020 ; Yan et al, 2021 ), stem cell signaling ( Davidson et al, 2007 ; Bijlmakers, 2009 ), and epithelial–mesenchymal transition ( Pastushenko et al, 2021 ; Wang et al, 2021 ). Based on these experimental and bioinformatics analyses, we hypothesized that HPV16 E6 and E7 signaling causes differential mRNA expression through direct or indirect mRNA pathways that regulate cell adhesion and chemokine secretion.…”

Reporting the Anti-neuroinflammatory Potential of Selected Spondias mombin Flavonoids through Network Pharmacology and Molecular Dynamics Simulations

“…Additionally, its potential as a target for Alzheimer's disease and cancer has been highlighted (Sil and Ghosh., 2016;Pu et al, 2021). FYN, a tyrosine kinase, plays a signi cant role in neuroin ammatory processes, cell proliferation, differentiation, and adhesion, and its expression has been reported in various cancer types (Marotta et al, 2022;Saminathan et al, 2020;Elias et al, 2015).…”