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Role of Fyn Kinase Inhibitors in Switching Neuroinflammatory Pathways

Giambattista Marotta1, Filippo Basagni1, Michela Rosini1

  • 1Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, via Belmeloro 6, Bologna, 40126, Italy.

Current Medicinal Chemistry
|December 23, 2021
PubMed

Insights

Fyn kinase, implicated in cancer and neurodegenerative diseases like Alzheimer's, is a promising therapeutic target. Developing selective Fyn inhibitors is challenging due to kinase homology, but recent efforts show potential for neurodegeneration treatment.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Oncology

Background:

  • Fyn kinase, a member of the Src family, regulates crucial cellular processes including proliferation, differentiation, adhesion, and motility.
  • Dysregulation and overexpression of Fyn kinase are observed in various cancers and neuroinflammatory conditions.
  • Fyn kinase plays significant roles in the central nervous system, including axon-glial signaling, oligodendrocyte maturation, and myelination.

Purpose of the Study:

  • To review recent advancements in identifying and optimizing small molecule Fyn inhibitors over the past decade.
  • To explore Fyn kinase as a therapeutic target for cancer and neurodegenerative diseases, particularly Alzheimer's disease (AD).
  • To discuss the challenges associated with Fyn inhibition, such as off-target effects due to kinase homology, and potential solutions like drug repositioning.

Main Methods:

  • Literature review of studies published in the last decade focusing on Fyn kinase inhibitors.
  • Analysis of enzymatic and cell-based assays used to evaluate Fyn inhibitor efficacy.
  • Examination of drug repositioning strategies for potential Fyn-targeted therapies.

Main Results:

  • Fyn kinase is activated by amyloid-beta (Aβ) via cellular prion protein and interacts with tau protein, implicating it in Alzheimer's disease pathogenesis.
  • Numerous small molecules targeting Fyn kinase have been developed and optimized.
  • Challenges remain in achieving Fyn selectivity due to high homology with other kinases, leading to off-target effects.

Conclusions:

  • Fyn kinase represents a significant therapeutic target for both cancer and neurodegenerative diseases, especially Alzheimer's disease.
  • Despite challenges with selectivity, ongoing research and drug repositioning offer opportunities for developing effective Fyn-based therapies for neurodegeneration.
  • Targeting Fyn kinase holds promise for novel therapeutic interventions in oncology and neurology.
Keywords:
Fyn kinasedasatinibfyn inhibitorsneurodegenerationpyrrolopyrimidinetyrosine kinase

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