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Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241419/ https://www.ncbi.nlm.nih.gov/pubmed/35799505 http://dx.doi.org/10.4103/1673-5374.340406 |
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author | Noh, Brian McCullough, Louise D. Moruno-Manchon, Jose F. |
author_facet | Noh, Brian McCullough, Louise D. Moruno-Manchon, Jose F. |
author_sort | Noh, Brian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9241419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-92414192022-06-30 Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome Noh, Brian McCullough, Louise D. Moruno-Manchon, Jose F. Neural Regen Res Review 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. Wolters Kluwer - Medknow 2022-04-25 /pmc/articles/PMC9241419/ /pubmed/35799505 http://dx.doi.org/10.4103/1673-5374.340406 Text en Copyright: © Neural Regeneration Research https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Review Noh, Brian McCullough, Louise D. Moruno-Manchon, Jose F. Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome |
title | Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome |
title_full | Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome |
title_fullStr | Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome |
title_full_unstemmed | Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome |
title_short | Sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome |
title_sort | sex-biased autophagy as a potential mechanism mediating sex differences in ischemic stroke outcome |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241419/ https://www.ncbi.nlm.nih.gov/pubmed/35799505 http://dx.doi.org/10.4103/1673-5374.340406 |
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