Title:Role of Fyn Kinase Inhibitors in Switching Neuroinflammatory Pathways
Volume: 29
Issue: 27
关键词:
Fyn激酶，神经变性，达沙替尼，酪氨酸激酶，fyn抑制剂，吡咯嘧啶。
摘要: 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.
