Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics

Amir Ajoolabady, Shuyi Wang, Guido Kroemer, Josef M. Penninger, Vladimir N. Uversky, Domenico Pratico, Nils Henninger, Russel J. Reiter, Askiel Bruno, Kaumudi Joshipura, Hamid Aslkhodapasandhokmabad, Daniel J. Klionsky, Jun Ren

Research output: Contribution to journalReview articlepeer-review

97 Scopus citations

Abstract

Stroke constitutes the second leading cause of death and a major cause of disability worldwide. Stroke is normally classified as either ischemic or hemorrhagic stroke (HS) although 87% of cases belong to ischemic nature. Approximately 700,000 individuals suffer an ischemic stroke (IS) in the US each year. Recent evidence has denoted a rather pivotal role for defective macroautophagy/autophagy in the pathogenesis of IS. Cellular response to stroke includes autophagy as an adaptive mechanism that alleviates cellular stresses by removing long-lived or damaged organelles, protein aggregates, and surplus cellular components via the autophagosome-lysosomal degradation process. In this context, autophagy functions as an essential cellular process to maintain cellular homeostasis and organismal survival. However, unchecked or excessive induction of autophagy has been perceived to be detrimental and its contribution to neuronal cell death remains largely unknown. In this review, we will summarize the role of autophagy in IS, and discuss potential strategies, particularly, employment of natural compounds for IS treatment through manipulation of autophagy.

Original languageEnglish (US)
Article number107848
JournalPharmacology and Therapeutics
Volume225
DOIs
StatePublished - Sep 2021

Keywords

  • Adaptive autophagy
  • Cell death
  • Cerebral I/R injury
  • Ischemic stroke
  • Maladaptive autophagy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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