Pathological Mechanism of Neuronal Autophagy Flow Disturbance Caused by NSF ATPase Inactivation After Cerebral Ischemia / 生物化学与生物物理进展

Cerebral ischemic stroke is an acute cerebrovascular disease caused by cerebral vascular occlusion, and it is associated with high incidence, disability, and mortality rates. Studies have found that excessive or insufficient autophagy can lead to cellular damage. Autophagy consists of autophagosome formation and maturation, autophagosome-lysosome fusion, degradation and clearance of autophagic substrates within autolysosomes, and these processes collectively constitute autophagic flux. Research has revealed that cerebral ischemia can induce impaired fusion between autophagosomes and lysosomes, resulting in autophagic flux impairment. Intracellular membrane fusion is mediated by three core components: N-ethylmaleimide sensitive factor (NSF) ATPase, soluble NSF attachment protein (SNAP), and soluble NSF attachment protein receptors (SNAREs). SNAREs, after mediating fusion between autophagosomes and lysosomes, remain in an inactive complex state on the autolysosomal membrane, requiring NSF reactivation into monomers to perform subsequent rounds of membrane fusion-mediated functions. NSF is the sole ATPase capable of reactivating SNAREs. Recent studies have shown that cerebral ischemia significantly inhibits NSF ATPase activity, reducing its reactivation of SNAREs. This may be a pathological mechanism for impaired fusion between autophagosomes and lysosomes, leading to neuronal autophagic flux impairment. This article discusses the pathological mechanisms of NSF ATPase inactivation, including SNAREs dysregulation, impaired fusion between autophagosomes and lysosomes, and insufficient transport of proteolytic enzymes to lysosomes, and explores approaches to improve neuronal autophagic flux through NSF ATPase reactivation. It provides references for stroke treatment improvement and points out directions for further research.

JNK-mediated Neuroprotective Mechanism after Ischemic Stroke in Rats / 中国生物化学与分子生物学报

In order to explore the protective mechanism of stress-activated protein kinase JNK on neurons after ischemic stroke,the model of middle cerebral artery occlusion (MCAO) in male SD rats was established by suture methods. Anisomycin (AN), a JNK agonist, was added at the characteristic time point of autophagy, and then Western blotting and immunofluorescence were used to detect the protein expression of autophagy flow pathways in ischemic penumbra, and the effects of JNK on the stability of Bcl-2-Beclin1 complex and autophagy flow pathway were analyzed. The results showed that compared with the MCAO+Veh group, the expression levels of LC3 (