Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy

Abstract

Stroke is one of the leading causes of death and disability worldwide. Autophagy is a conserved cellular catabolic pathway that maintains cellular homeostasis by removal of damaged proteins and organelles, which is critical for the maintenance of energy and function homeostasis of cells. Accumulating evidence demonstrates that autophagy plays important roles in pathophysiological mechanisms under ischemic stroke. Previous investigations show that autophagy serves as a “double-edged sword” in ischemic stroke as it can either promote the survival of neuronal cells or induce cell death in special conditions. Following ischemic stroke, autophagy is activated or inhibited in several cell types in brain, including neurons, astrocytes, and microglia, as well as microvascular endothelial cells, which involves in inflammatory activation, modulation of microglial phenotypes, and blood-brain barrier permeability. However, the exact mechanisms of underlying the role of autophagy in ischemic stroke are not fully understood. This review focuses on the recent advances regarding potential molecular mechanisms of autophagy in different cell types. The focus is also on discussing the “double-edged sword” effect of autophagy in ischemic stroke and its possible underlying mechanisms. In addition, potential therapeutic strategies for ischemic stroke targeting autophagy are also reviewed.

HABP2 Encapsulated by Peripheral Blood-Derived Exosomes Suppresses Astrocyte Autophagy to Exacerbate Neuroinflammatory Injury in Mice with Ischemic Stroke

“…Autophagy plays a significant role in IS . On the one hand, inflammasome activation can alleviate cerebral ischemic injury by disrupting autophagy activation.…”

“…Autophagy plays a significant role in IS. 21 On the one hand, inflammasome activation can alleviate cerebral ischemic injury by disrupting autophagy activation. On the other hand, autophagy activation inhibits ischemia-caused neuroinflammation and serves as a cellular protective mechanism, while inflammation is a defense mechanism, both of which jointly respond to ischemic brain damage.…”

Microglia Autophagy Mediated by TMEM166 Promotes Ischemic Stroke Secondary to Carotid Artery Stenosis

“…Recent studies have demonstrated that autophagy is involved in the death of various cells after stroke [ 5 - 7 ], including microglia [ 8 - 9 ]. However, the role and potential mechanisms of microglial autophagy in ischemic stroke after CEA remain unclear.…”

Hemiplegia in acute ischemic stroke: A comprehensive review of case studies and the role of intravenous thrombolysis and mechanical thrombectomy

“…Several reviews have been conducted recently in the field of stroke management, 43 focusing on topics such as early recognition, 44 , 45 , 46 , 47 , 48 novel therapeutics, 49 , 50 , 51 comparison of thrombolytic agents, 52 combination of MT with IVT, 53 and safety and efficacy of IVT after antagonization of unfractionated heparin with protamine, 54 among others. This review critically assesses IVT versus MT within a 4.5‐h window, considering pretreatment and posttreatment NIHSS scales—an aspect overlooked in current literature.…”