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Published on: December 7, 2014
Fyn kinase in brain diseases and cancer: the search for inhibitors
S Schenone1, C Brullo, F Musumeci
1Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV, 3, I-16132, Genova, Italy. schensil@unige.it
Abstract:
Fyn is a non-receptor tyrosine kinase belonging to the Src family kinases. It has been shown to play important roles in neuronal functions, including myelination and oligodendrocytes formation, and in inflammatory processes. It has also demonstrated its involvement in signaling pathways that lead to severe brain pathologies, such as Alzheimer's and Parkinson's diseases. Moreover, Fyn is upregulated in some malignancies. Experimental studies demonstrated that Fyn inhibition could be useful in the disruption of metabolic processes involved in cancer neurodegenerative diseases. Unfortunately, no specific Fyn inhibitor has been discovered till today, active compounds on other members of Src family or on different tyrosine kinases have also been reported. However, multitargeted inhibitors might be endowed with therapeutic potential. Indeed, as increasingly reported, also a not completely selective inhibitor of a specific protein could be therapeutically useful, affecting a number of cell pathways involved especially in cancer development. In this review, we report some examples of small molecule tyrosine kinase inhibitors for which data on Fyn inhibition, both in enzymatic and in cell assays, have been reported, with the aim of giving information as starting point for the researchers working in this field.
Insights
Fyn kinase is implicated in brain diseases and cancer. This review highlights small molecule inhibitors targeting Fyn, offering potential therapeutic strategies for neurodegenerative conditions and malignancies.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Fyn is a non-receptor tyrosine kinase in the Src family.
- It plays roles in neuronal functions (myelination, oligodendrocyte formation) and inflammation.
- Fyn is linked to Alzheimer's, Parkinson's diseases, and upregulated in malignancies.
Purpose of the Study:
- To review small molecule tyrosine kinase inhibitors targeting Fyn.
- To provide a starting point for researchers investigating Fyn inhibition.
Main Methods:
- Literature review of experimental studies.
- Analysis of enzymatic and cell-based assays for Fyn inhibition.
Main Results:
- No specific Fyn inhibitors are currently available.
- Some compounds inhibit other Src family kinases or different tyrosine kinases.
- Multitargeted inhibitors show therapeutic potential for cancer and neurodegenerative diseases.
Conclusions:
- Fyn inhibition is a promising therapeutic strategy.
- Small molecule inhibitors targeting Fyn, even non-selective ones, warrant further investigation.
- This review compiles relevant inhibitors for future research.
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