Role of Fyn Kinase Inhibitors in Switching Neuroinflammatory Pathways.

Giambattista Marotta, Filippo Basagni, Michela Rosini, Anna Minarini

Current medicinal chemistry 2022

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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's 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 for therapeutic intervention in neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

Giambattista Marotta, Filippo Basagni, Michela Rosini, Anna Minarini. Role of Fyn Kinase Inhibitors in Switching Neuroinflammatory Pathways. Current medicinal chemistry. 2022;29(27):4738-4755