FUS aggregation following ischemic stroke favors brain astrocyte activation through inducing excessive autophagy

Wu, Shusheng; Yin, Yuye; Du, Longfei

doi:10.1016/j.expneurol.2022.114144

Cited by 4 publications

(3 citation statements)

References 78 publications

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“…This astroglial activation might not be a consequence of active inflammation for a degeneration process, since there is no transcriptional profile related to active cell death in any of the analysis. It has been shown that FUS aggregation causes brain astrocyte activation following ischemic stroke damage (64). A study showed that the expression of another human mutant form of FUS (P525L-FUS), which is also associated with early onset ALS, drives neuronal progenitor cells preferentially towards a glial lineage, strongly reducing the number of developing neurons (45).…”

Section: Discussionmentioning

confidence: 99%

FUSDelta14 mutation impairs normal brain development and causes systemic metabolic alterations

Godoy-Corchuelo

Ali

Martins-Bach

et al. 2023

Preprint

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FUS (Fused in sarcoma) is a ubiquitously expressed RNA binding protein, which is mislocalized and aggregated in some forms of frontotemporal dementia (FTD), whilst mutations in FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS), as in the case with the FUSDelta14 mutation. Most studies have focused on the role of FUS in motor neuron degeneration, although it is unknown whether FUS mutations affect other cell and tissue types, and the neurodevelopmental impact of FUS mutation on the nervous system is unclear. Here we studied pleiotropic phenotypes in a physiological knock-in mouse model carrying a partially humanised FUSDelta14 mutation in homozygosity. We performed RNA sequencing of six different tissues (frontal cortex, spinal cord, tibialis anterior muscle, white and brown adipose tissue and liver) and found that the genes and pathways affected were generally tissue-specific and showed few commonalities. Phenotypic assessment of homozygous FUSDelta14 mice revealed systemic metabolic alterations related to the pathway changes identified. Homozygous FUSDelta14 brains displayed significant morphological alterations including a thinner cortex, reduced neuronal number and increased gliosis, which correlated with fatal seizures in early adult life. Altogether, our data supports a wide-ranging role for FUS, and suggests that the disease aetiology of FUS mutation can include developmental and pleiotropic phenotypes.

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Section: Discussionmentioning

confidence: 99%

FUSDelta14 mutation impairs normal brain development and causes systemic metabolic alterations

Godoy-Corchuelo

Ali

Martins-Bach

et al. 2023

Preprint

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“…The interaction of microglial and astrocytes jointly participates in the formation of glial scar which is the barrier for axonal regrowth and functional recovery in the late times of ischemic stroke [51], in which astrocytes are activated [52]. Wu et al [53] reported that fused in sarcoma induced excessive autophagy and activated astrocytes which was a new target for improving the outcome after stroke.…”

Section: Glial Autophagy In Ischemic Strokementioning

confidence: 99%

Autophagy in ischemic stroke: role of circular RNAs

Hong,

Gu,

Han

et al. 2023

Exploration of Medicine

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Stroke, a central nervous system (CNS) injury, is responsible for the second leading cause of death in the world, bringing a great burden on the world. Stroke is normally divided into ischemic and hemorrhagic stroke, among which ischemic stroke takes up 87% proportion. Accumulating evidence has denoted a rather pivotal role for autophagy in the pathogenesis of ischemic stroke, which is activated in neuronal cells, glial cells, and endothelial cells. Besides, circular RNAs (circRNAs), a novel type of epigenetic regulation, are highly expressed in the CNS and are involved in the process of CNS diseases, which is regarded as an important molecular mechanism in ischemic stroke. Meanwhile, circRNA and autophagy have a significant correlation. The intracellular signaling pathways regulating autophagy can either restrain or activate autophagy. However, under the circumstances of ischemic stroke, the precise communication between circRNA and stroke is largely unknown. This review aims to provide a summary of the relationship between circRNA, autophagy, and ischemic stroke, as well as the current research advancements in understanding how circRNA regulates autophagy in the context of stroke.

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“…Notably, there is a shift from a UPS to an autophagy-mediated protein degradation pathway from ischemic injury to severe injury ( 52 ). Impaired UPS capacity in cerebral ischemia leads to the activation of compensatory astrocyte autophagy by massive fused in sarcoma (FUS) aggregate and may lead to excessive autophagy ( 130 ). Therefore, there are interactions and crosstalk between UPSs and autophagy in ischemic astrocytes, and how to use the mechanism and relationship to treat an ischemic injury is a new challenge.…”

Section: Crosstalk Between Astrocyte Autophagy and Other Mechanisms I...mentioning

confidence: 99%

Research progress on astrocyte autophagy in ischemic stroke

Zhai

Wang

et al. 2022

Front. Neurol.

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Ischemic stroke is a highly disabling and potentially fatal disease. After ischemic stroke, autophagy plays a key regulatory role as an intracellular catabolic pathway for misfolded proteins and damaged organelles. Mounting evidence indicates that astrocytes are strongly linked to the occurrence and development of cerebral ischemia. In recent years, great progress has been made in the investigation of astrocyte autophagy during ischemic stroke. This article summarizes the roles and potential mechanisms of astrocyte autophagy in ischemic stroke, briefly expounds on the crosstalk of astrocyte autophagy with pathological mechanisms and its potential protective effect on neurons, and reviews astrocytic autophagy-targeted therapeutic methods for cerebral ischemia. The broader aim of the report is to provide new perspectives and strategies for the treatment of cerebral ischemia and a reference for future research on cerebral ischemia.

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FUS aggregation following ischemic stroke favors brain astrocyte activation through inducing excessive autophagy

Cited by 4 publications

References 78 publications

FUSDelta14 mutation impairs normal brain development and causes systemic metabolic alterations

FUSDelta14 mutation impairs normal brain development and causes systemic metabolic alterations

Autophagy in ischemic stroke: role of circular RNAs

Research progress on astrocyte autophagy in ischemic stroke

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