Role of Fyn Kinase Inhibitors in Switching Neuroinflammatory Pathways.
Fyn kinase
dasatinib
fyn inhibitors
neurodegeneration
pyrrolopyrimidine
tyrosine kinase
Journal
Current medicinal chemistry
ISSN: 1875-533X
Titre abrégé: Curr Med Chem
Pays: United Arab Emirates
ID NLM: 9440157
Informations de publication
Date de publication:
2022
2022
Historique:
received:
30
07
2021
revised:
18
11
2021
accepted:
22
11
2021
pubmed:
24
12
2021
medline:
19
8
2022
entrez:
23
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34939537
pii: CMC-EPUB-119579
doi: 10.2174/0929867329666211221153719
doi:
Substances chimiques
Proto-Oncogene Proteins c-fyn
EC 2.7.10.2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4738-4755Subventions
Organisme : Italian Ministry of University and Research (MIUR), PRIN 2017
ID : 2017MT3993_007
Informations de copyright
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