Mst1: Function and Mechanism in Brain and Myocardial Ischemia Reperfusion Injury

Abstract

Mammalian STE20-like kinase-1 (Mst1) is a generally expressed apoptosis-promoting kinase and a key bridgebuilder of apoptotic signaling in the etiology of tissue injury. Despite the fact that the biological function of Mst1 and its role in the cell's signalling network have yet to be determined, however, there is a lot of evidence that Mst1 plays an important role in cell death which results from tissue injury. Previous studies have shown that Mst1 is not only a target for some apoptosis- related molecules such as caspase 3 and P53, but also act as an activator of these proteinases to magnify apoptosis signal pathways. This article reviews the role of Mst1 in the signaling pathways which is related with the neuronal cell apoptosis or microglia activation following myocardial and brain injury. Therefore, this work contributes to better understanding of the pathological process of myocardial and brain injury.

Hederagenin Attenuates Cerebral Ischaemia/Reperfusion Injury by Regulating MLK3 Signalling

“…Our results show that HE improves the neurological behavior function and decreases the infarct volumes of mice after CI/R injury. Apoptosis and inflammation are the main pathological mechanisms of CI/R injury ( Su et al, 2017 ; Li et al, 2018 ). Local ischaemia first leads to neuronal apoptosis ( Zhang C. Y. et al, 2019 ).…”

HIF‑1α in myocardial ischemia‑reperfusion injury (Review)

“…Cardiomyocyte death may be promoted by a number of synergistic mechanisms throughout the pathophysiological process. Numerous molecular targets associated with MIRI and cardioprotection have been identified ( 86 , 87 ). HIF-1α is one of the most promising targets ( 88 ).…”

Mechanosensing and the Hippo Pathway in Microglia: A Potential Link to Alzheimer’s Disease Pathogenesis?

“…However, when the brain microenvironment is compromised, due to altered homeostasis or damage [20], microglia migrate to affected regions, proliferate, adopt an amoeboid shape, and change their phenotype to an 'activated' state to increase both phagocytosis of cellular debris and expression of inflammatory mediators [21] (Figure 1). Eventually, activated microglia cells experience apoptosis by an activation-induced cell death (AICD) process [22,23].…”

“…The inhibition of MST1 in microglia suppressed NF-κB signalling and microglial activation (Figure 2), showing that MST1 has a protective function in microglia-induced neuroinflammation. MST1 signalling and kinase activity is activated in this microglial context by upstream key signalling molecules such as Src, c-Abl and Daxx [23,75] (Figure 2). Src kinase was found to directly phosphorylate the tyrosine 433 site of MST1, leading to MST1 activation and thus regulating MST1-IκBα signalling throughout microglial activation [23,75] (Figure 2).…”

“…MST1 signalling and kinase activity is activated in this microglial context by upstream key signalling molecules such as Src, c-Abl and Daxx [23,75] (Figure 2). Src kinase was found to directly phosphorylate the tyrosine 433 site of MST1, leading to MST1 activation and thus regulating MST1-IκBα signalling throughout microglial activation [23,75] (Figure 2). Hence, the Src-MST1-IκBα signalling axis is a significant player in neuronal death via microglial activation (59).…”