IRE1α inhibition attenuates neuronal pyroptosis via miR-125/NLRP1 pathway in a neonatal hypoxic-ischemic encephalopathy rat model

Huang, Juan; Lu, WW; Doycheva, Desislava; Gamdzyk, Marcin; Xiao, Hu; Li, Rui; Zhang, Junyi; Tang, Jiping

doi:10.1186/s12974-020-01796-3

Cited by 47 publications

(23 citation statements)

References 72 publications

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“…The nucleotide‐binding oligomerization domain (NOD)‐like receptor (NLR) pyrin domain‐containing (NLRP) inflammasomes activate the cleavage of pro‐interleukin‐1β (pro‐IL‐1β) and pro‐IL‐18, based on caspase‐1 and trigger pyroptosis (Huang et al, 2020). Recently, it was reported that pyroptosis is widespread in diseases of the central nervous system, which is involved in the repair, aging, tumor, cerebral hemorrhage, and ischemia of the central nervous system (Huang et al, 2020; Q. Li et al, 2020; Sun et al, 2020). However, the precise role of pyroptosis and related regulation drugs in SAH has not been confirmed.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation

Chen

Zhang

Yan

et al. 2021

Journal Cellular Physiology

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Subarachnoid hemorrhage (SAH) is a subtype of stroke with high mortality and morbidity due to the lack of effective therapy. Atorvastatin has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH) via reducing reactive oxygen species, antiapoptosis, regulated autophagy, and neuroinflammation. Which was the related to the pyroptosis? Pyroptosis can be defined as a highly specific inflammatory programmed cell death, distinct from classical apoptosis and necrosis. However, the precise role of pyroptosis in atorvastatin‐mediated neuroprotection following SAH has not been confirmed. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of atorvastatin in the SAH‐induced EBI via regulating neural pyroptosis using the filament perforation model of SAH in male C57BL/6 mice, and the hemin‐induced neuron damage model in HT‐22. Atorvastatin or vehicle was administrated 2 h after SAH and hemin‐induced neuron damage. The mortality, neurological score, brain water content, and neuronal death were evaluated. The results show that the atorvastatin treatment markedly increased survival rate, neurological score, greater survival of neurons, downregulated the protein expression of NLRP1, cleaved caspase‐1, interleukin‐1β (IL‐1β), and IL‐18, which indicated that atorvastatin‐inhibited pyroptosis and neuroinflammation, ameliorated neuron death in vivo/vitro subjected to SAH. Taken together, this study demonstrates that atorvastatin improved the neurological outcome in rats and reduced the neuron death by against neural pyroptosis and neuroinflammation.

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Section: Introductionmentioning

confidence: 99%

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation

Chen

Zhang

Yan

et al. 2021

Journal Cellular Physiology

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“…Some previous studies have confirmed that pyroptosis inhibition had positive impacts on the prognosis of HIE. In one study, an IRE1α inhibitor was proven to protect HIE rats by inactivating the NLRP1/caspase-1 pathway, and the NLRP1 activator CRISPR, which was used to activate NLRP1, offsets the protective effects of an IRE1α inhibitor [35]. In another study, it was shown that TIGAR played a protective role in neonatal HIBD by inhibiting microglial pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

Spinal Tuina Improves Cognitive Impairment in Cerebral Palsy Rats through Inhibiting Pyroptosis Induced by NLRP3 and Caspase-1

Niu

Wang

Zhong

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Cerebral palsy (CP) is a severe cerebral disease with high mortality and morbidity, which leads to great challenges for the suffering children and their families. Hence, the need for the efficacious and safe treatments is urgent. As a physical therapy arising from traditional Chinese medicine (TCM), Tuina has shown multiple effects on various diseases, including cerebral palsy. Nevertheless, the detailed mechanisms of Tuina on CP remain unknown, which impedes its further clinical application. Herein, we explored the effects of Tuina on CP and its potential mechanisms. Thirty Sprague Dawley (SD) male rats were randomly divided into sham, model, and Tuina groups (model + Tuina). CP rat model was established by hypoxia-ischemia via permanent occlusion of left common carotid artery and hypoxia for 2.5 hours caused by anaerobic environment, which was subsequently followed by onset of Tuina treatment from postnatal day 7 (P7) to P49. After completion of Tuina treatment, the behavioral tests showed that Tuina treatment not only improved the retarded body weight and impaired motor balance function, but also ameliorated weakened learning and memory function of CP rats. Moreover, immunohistochemistry and western blot also revealed a reduced expression of NLRP3 inflammasome and corresponding pyroptosis-related molecules induced by NLRP3 in CP rats after Tuina treatment. Therefore, our study indicated that Tuina treatment may improve impaired neurocognitive function of CP rats, which was possibly realised via inhibiting NLRP3-induced pyroptosis.

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“…Consistent with this observation, in the cerebral venous sinus thrombosis (CVST) model, p-PERK and p-IRE1α were found to be expressed primarily in neurons; they contributed to neuronal pyroptosis by regulating TXNIP–NLRP3 inflammasome activation ( 72 ). In addition, recent research demonstrated that IRE1α could modulate NLRP1 inflammasome-mediated neuronal pyroptosis by regulating the expression of miR-125-b-2-3p ( 73 ). PERK inhibition has been reported to inhibit NLRP3 inflammasome activation by regulating the mitochondria-associated endoplasmic reticulum membrane (MAM)-induced calcium release ( 74 ).…”

Section: Role Of Endoplasmic Reticulum Stress In Neuronal Deathmentioning

confidence: 99%

Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases

Shi

Chai²,

Zhang

et al. 2022

Front. Immunol.

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Neuronal death and inflammatory response are two common pathological hallmarks of acute central nervous system injury and chronic degenerative disorders, both of which are closely related to cognitive and motor dysfunction associated with various neurological diseases. Neurological diseases are highly heterogeneous; however, they share a common pathogenesis, that is, the aberrant accumulation of misfolded/unfolded proteins within the endoplasmic reticulum (ER). Fortunately, the cell has intrinsic quality control mechanisms to maintain the proteostasis network, such as chaperone-mediated folding and ER-associated degradation. However, when these control mechanisms fail, misfolded/unfolded proteins accumulate in the ER lumen and contribute to ER stress. ER stress has been implicated in nearly all neurological diseases. ER stress initiates the unfolded protein response to restore proteostasis, and if the damage is irreversible, it elicits intracellular cascades of death and inflammation. With the growing appreciation of a functional association between ER stress and neurological diseases and with the improved understanding of the multiple underlying molecular mechanisms, pharmacological and genetic targeting of ER stress are beginning to emerge as therapeutic approaches for neurological diseases.

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IRE1α inhibition attenuates neuronal pyroptosis via miR-125/NLRP1 pathway in a neonatal hypoxic-ischemic encephalopathy rat model

Cited by 47 publications

References 72 publications

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation

Spinal Tuina Improves Cognitive Impairment in Cerebral Palsy Rats through Inhibiting Pyroptosis Induced by NLRP3 and Caspase-1

Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases

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