中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 31-37.doi: 10.4103/1673-5374.340406

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

性别不均自噬作为介导缺血性卒中结果性别差异的潜在机制

  

  • 出版日期:2023-01-15 发布日期:2022-06-16

Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome

Brian Noh, Louise D. McCullough, Jose F. Moruno-Manchon*   

  1. Department of Neurology, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA
  • Online:2023-01-15 Published:2022-06-16
  • Contact: Jose F. Moruno-Manchon, PhD, Jose.felix.morunomanchon@uth.tmc.edu.
  • Supported by:
    This work was supported by the American Heart Association (856061) to JFMM and by the NINDS (R01 5R01NS108779 and 5R01NS094543) to LDM.

摘要: https://orcid.org/0000-0002-2139-6134 (Jose F. Moruno-Manchon)

Abstract: Stroke is the second leading cause of death and a major cause of disability worldwide, and biological sex is an important determining factor in stroke incidence and pathology. From childhood through adulthood, men have a higher incidence of stroke compared with women. Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke. Autophagy is a self-degrading cellular process orchestrated by multiple core proteins, which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy vesicles fuse with lysosomes or endosomes. The levels and the activity of components of these signaling pathways and of autophagy-related proteins can be altered during ischemic insults. Ischemic stroke activates autophagy, however, whether inhibiting autophagy after stroke is beneficial in the brain is still under a debate. Autophagy is a potential mechanism that may contribute to differences in stroke progression between the sexes. Furthermore, the effects of manipulating autophagy may also differ between the sexes. Mechanisms that regulate autophagy in a sex-dependent manner in ischemic stroke remain unexplored. In this review, we summarize clinical and pre-clinical evidence for sex differences in stroke. We briefly introduce the autophagy process and summarize the effects of gonadal hormones in autophagy in the brain and discuss X-linked genes that could potentially regulate brain autophagy. Finally, we review pre-clinical studies that address the mechanisms that could mediate sex differences in brain autophagy after stroke.

Key words: autophagy, brain, estrogen, gonadal hormones, neurodegeneration, neuron, stroke, X-chromosome