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Background <p>The role of autophagy following stroke and its underlying cascades have not yet been investigated in detail. The ischemic brain is characterized by complex pathophysiological mechanisms, including increased excitotoxicity, oxidative stress, inflammatory responses, intrinsic and extrinsic apoptotic pathways, blood-brain barrier (BBB) integrity, neurotoxic proteins, and neurodegeneration. By engaging multiple molecular pathways, autophagy plays both protective and detrimental roles in ischemic stroke. <b>Main text</b>: This review explores the state-of-the-art regarding autophagy’s role in neurotoxic protein clearance, neuroinflammation, oxidative stress, BBB, and neural tissue regeneration during and after ischemic stroke. Additionally, neuroinflammation is modulated by autophagy such that the inflammasomes and proinflammatory complexes that cause post-ischemic neuroinflammation are degraded. However, autophagy can be dysregulated, resulting in chronic neuro-inflammation. Moreover to counteract the excessive oxidative stress, autophagy is triggered mainly through the PINK1/Parkin pathway. In contrast, over-activated autophagy may cause neuronal damage and cell death. Autophagy maintains BBB integrity by restoring tight junction proteins. However, if dysregulated, the infiltration of inflammatory neurotoxic substances can exacerbate ischemic injury, highlighting the need for balanced regulation of autophagy. As the central nervous system (CNS) has limited regenerative capability, neural stem and progenitor cells are activated to promote neurogenesis following stroke. Autophagy can also enhance those regenerative processes. <b>Conclusions</b> Modulating autophagy offers potential therapeutic strategies in stroke patients by enhancing the protective effects of autophagy while minimizing its harmful consequences.</p> Graphical abstract <p></p>

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Role of autophagy in neurotoxic protein’s clearance following post-ischemic stroke: where we are and what we know?

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月8日

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  • Sareh Kazmi,
  • Fatemeh Farokhi-Sisakht,
  • Samin Davoody,
  • Gozal Bahlakeh,
  • Fatemeh Abbaszadeh,
  • Reza Rahbarghazi,
  • Aliakbar Shekarchi,
  • Mohammad Karimipour

摘要

Background

The role of autophagy following stroke and its underlying cascades have not yet been investigated in detail. The ischemic brain is characterized by complex pathophysiological mechanisms, including increased excitotoxicity, oxidative stress, inflammatory responses, intrinsic and extrinsic apoptotic pathways, blood-brain barrier (BBB) integrity, neurotoxic proteins, and neurodegeneration. By engaging multiple molecular pathways, autophagy plays both protective and detrimental roles in ischemic stroke. Main text: This review explores the state-of-the-art regarding autophagy’s role in neurotoxic protein clearance, neuroinflammation, oxidative stress, BBB, and neural tissue regeneration during and after ischemic stroke. Additionally, neuroinflammation is modulated by autophagy such that the inflammasomes and proinflammatory complexes that cause post-ischemic neuroinflammation are degraded. However, autophagy can be dysregulated, resulting in chronic neuro-inflammation. Moreover to counteract the excessive oxidative stress, autophagy is triggered mainly through the PINK1/Parkin pathway. In contrast, over-activated autophagy may cause neuronal damage and cell death. Autophagy maintains BBB integrity by restoring tight junction proteins. However, if dysregulated, the infiltration of inflammatory neurotoxic substances can exacerbate ischemic injury, highlighting the need for balanced regulation of autophagy. As the central nervous system (CNS) has limited regenerative capability, neural stem and progenitor cells are activated to promote neurogenesis following stroke. Autophagy can also enhance those regenerative processes. Conclusions Modulating autophagy offers potential therapeutic strategies in stroke patients by enhancing the protective effects of autophagy while minimizing its harmful consequences.

Graphical abstract