Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications

Abstract

Ischemic stroke caused by arterial occlusion is the most common type of stroke and is one of the leading causes of disability and death, with the incidence increasing each year. Fyn is a nonreceptor tyrosine kinase belonging to the Src family of kinases (SFKs), which is related to many normal and pathological processes of the nervous system, including neurodevelopment and disease progression. In recent years, more and more evidence suggests that Fyn may be closely related to cerebral ischemia-reperfusion, including energy metabolism disorders, excitatory neurotoxicity, intracellular calcium homeostasis, free radical production, and the activation of apoptotic genes. This paper reviews the role of Fyn in the pathological process of cerebral ischemia-reperfusion, including neuroexcitotoxicity and neuroinflammation, to explore how Fyn affects specific signal cascades and leads to cerebral ischemia-reperfusion injury. In addition, Fyn also promotes the production of superoxide and endogenous NO, so as to quickly react to produce peroxynitrite, which may also mediate cerebral ischemia-reperfusion injury, which is discussed in this paper. Finally, we revealed the treatment methods related to Fyn inhibitors and discussed its potential as a clinical treatment for ischemic stroke.

Fat mass and obesity associated protein inhibits neuronal ferroptosis via the FYN/Drp1 axis and alleviate cerebral ischemia/reperfusion injury

“…Considering that FYN may regulate the process of cerebral I/R, 14 we also designed related experiments to ascertain the specific effects of FYN on cerebral I/R injury. It was reported that the shortage of FYN contributed to the suppression of OS in diabetic renal fibrosis.…”

“… 43 , 44 Our data proved that FYN was upregulated after tMCAO/R treatment and FTO overexpression reduced FYN expression by decreasing FYN mRNA m6A modification. Considering that FYN may regulate the process of cerebral I/R, 14 we also designed related experiments to ascertain the specific effects of FYN on cerebral I/R injury. It was reported that the shortage of FYN contributed to the suppression of OS in diabetic renal fibrosis.…”

“… 13 Importantly, FYN stimulates neuroinflammation and OS, thus irritating I/R injury. 14 However, the function of the FYN/Drp1 axis on ferroptosis in cerebral I/R injury warrants further investigations.…”

“…Belonging to the Src nonreceptor tyrosine kinase family, FYN exerts many functions in cellular processes and is related to inflammation in the central nervous system 13 . Importantly, FYN stimulates neuroinflammation and OS, thus irritating I/R injury 14 . However, the function of the FYN/Drp1 axis on ferroptosis in cerebral I/R injury warrants further investigations.…”

Exploring the benefits of in-diet versus repeated oral dosing of saracatinib (AZD0530) in chronic studies: insights into pharmacokinetics and animal welfare

“…Considering the role of Fyn/Src kinases in cell proliferation, saracatinib has been in clinical trials for various types of cancers, such as bone, ovarian, and breast cancer (7)(8)(9). Excessive production of Fyn/Src and its phosphorylation in reactive glial cells or neurons causes hyperexcitability, neuroinflammation, and neurodegeneration (10,11). Therefore, saracatinib has been tested as a disease modifier in experimental models of epilepsy and AD (3,12) and in clinical trials for AD and Parkinson's disease (13,14).…”