Shank3 ameliorates neuronal injury after cerebral ischemia/reperfusion via inhibiting oxidative stress and inflammation DOI Creative Commons

Hongchen Zhang,

Yuan Feng,

Yanfang Si

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 69, P. 102983 - 102983

Published: Dec. 5, 2023

Shank3, a key molecule related to the development and deterioration of autism, has recently been found downregulate in murine brain after ischemia/reperfusion (I/R). Despite this discovery, however, its effects on neuronal injury mechanism underlying remain be clarified. To address this, study, based genetically modified mice models, we revealed that expression Shank3 showed time-dependent change hippocampal neurons I/R, conditional knockout (cko) resulted aggravated injuries. The protective against oxidative stress inflammation I/R were achieved through direct binding STIM1 subsequent proteasome-mediated degradation STIM1. downregulation induced phosphorylation downstream Nrf2 Ser40, which subsequently translocated nucleus, further increased antioxidant genes such as NQO1 HO-1 HT22 cells. In vivo, study confirmed double Stim1 alleviated Shank3cko mice. conclusion, present demonstrated interacts with inhibits post-I/R inflammatory response via pathway. This interaction can potentially contribute promising method for treatment.

Language: Английский

Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke DOI Creative Commons

Rui Mao,

Ningning Zong,

Yujie Hu

et al.

Neuroscience Bulletin, Journal Year: 2022, Volume and Issue: 38(10), P. 1229 - 1247

Published: May 5, 2022

Abstract Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase thrombectomy. Even so, patients still benefit little due short therapeutic window risk of ischemia/reperfusion injury. It is therefore urgent figure out neuronal death mechanisms following ischemic in order develop new neuroprotective strategies. Regarding pathogenesis, multiple pathological events trigger activation cell pathways. Particular attention should be devoted excitotoxicity, oxidative stress, inflammatory responses. Thus, this article, we first review principal underlying mediated these significant events, such as intrinsic extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, autophagic death. Then, further discuss possibility interventions targeting summarize present pharmacological achievements.

Language: Английский

Citations

157
ER stress and UPR in Alzheimer’s disease: mechanisms, pathogenesis, treatments DOI Creative Commons
Amir Ajoolabady, Dan Lindholm, Jun Ren

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(8)

Published: Aug. 15, 2022

Abstract Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes heavy burden on the healthcare system globally. Current therapeutics to interfere with underlying process in AD still under development. Although many efforts have centered toxic forms Aβ effectively tackle AD, considering unsatisfactory results so far it vital examine other targets therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers build-up unfolded or misfolded proteins within ER, thus, perturbing ER cellular homeostasis. Emerging evidence indicates that contributes onset development AD. A thorough elucidation machinery pathology may help open up new avenues management this condition relieve dementia symptoms. Herein, we aim at deciphering unique role pathogenesis, reviewing key findings, existing controversy an attempt summarize plausible interventions pathophysiology.

Language: Английский

Citations

132
Mitophagy in cardiovascular diseases: molecular mechanisms, pathogenesis, and treatment DOI Creative Commons
Amir Ajoolabady, Mario Chiong, Sergio Lavandero

et al.

Trends in Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(10), P. 836 - 849

Published: July 22, 2022

Language: Английский

Citations

121
Interplay of energy metabolism and autophagy DOI
Yuyao Feng, Ying Chen,

Xiaoyong Wu

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 20(1), P. 4 - 14

Published: Aug. 18, 2023

Macroautophagy/autophagy, is widely recognized for its crucial role in enabling cell survival and maintaining cellular energy homeostasis during starvation or stress. Its regulation intricately linked to status. In this review, covering yeast, mammals, plants, we aim provide a comprehensive overview of the understanding roles mechanisms carbon- glucose-deprivation related autophagy, showing how cells effectively respond such challenges survival. Further investigation needed determine specific degraded substrates by autophagy glucose deprivation diverse varying durations starvation.

Language: Английский

Citations

65
Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects DOI Creative Commons

Qin Ru,

Yusheng Li,

Lin Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

Citations

50
The role of mitochondrial dynamics in cerebral ischemia-reperfusion injury DOI Open Access
Jie Huang, Lei Chen,

Zi‐Meng Yao

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114671 - 114671

Published: April 8, 2023

Stroke is one of the leading causes death and long-term disability worldwide. More than 80 % strokes are ischemic, caused by an occlusion cerebral arteries. Without question, restoration blood supply as soon possible first therapeutic strategy. Nonetheless paradoxically, reperfusion can further aggravate injury through a series reactions known ischemia-reperfusion (CIRI). Mitochondria play vital role in promoting nerve survival neurological function recovery mitochondrial dysfunction considered characteristics CIRI. Neurons often die due to oxidative stress imbalance energy metabolism following CIRI, there strong association with dysfunction. Altered dynamics reaction stress. Mitochondrial refers maintenance integrity, distribution, size mitochondria well their ability resist external stimuli continuous cycle fission fusion. Therefore, improving means treating This review discusses relationship between CIRI emphasizes potential approach improve prognosis

Language: Английский

Citations

44
Polystyrene Nanoplastics Activate Autophagy and Suppress Trophoblast Cell Migration/Invasion and Migrasome Formation to Induce Miscarriage DOI

Shukun Wan,

Xiaoqing Wang, Weina Chen

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 3733 - 3751

Published: Jan. 22, 2024

Nanoplastics (NPs), as emerging pollutants, have attracted global attention. Nevertheless, the adverse effects of NPs on female reproductive health, especially unexplained miscarriage, are poorly understood. Defects trophoblast cell migration and invasion associated with miscarriage. Migrasomes were identified cellular organelles largely unidentified functions. Whether might affect migration, invasion, migrasome formation induce miscarriage has been completely unexplored. In this study, we selected polystyrene nanoplastics (PS-NPs, 50 nm) a model plastic particles treated human cells pregnant mice PS-NPs at doses near actual environmental exposure in humans. We found that to induced mouse suppressed ROCK1-mediated migration/invasion formation. SOX2 was transcription factor ROCK1. activated autophagy promoted degradation SOX2, thus suppressing SOX2-mediated ROCK1 transcription. Supplementing murine or could efficiently rescue alleviate Analysis protein levels ROCK1, TSPAN4, NDST1, P62, LC-3BII/I PS-NP-exposed cells, villous tissues patients, placental gave consistent results. Collectively, study revealed toxicity their potential regulatory mechanism, indicating NP is risk for health.

Language: Английский

Citations

36
Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy DOI
Ting Zheng,

Taotao Jiang,

Hongxiang Ma

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 7930 - 7949

Published: March 5, 2024

Language: Английский

Citations

16
Mitophagy in Cerebral Ischemia and Ischemia/Reperfusion Injury DOI Creative Commons

Luoan Shen,

Qinyi Gan,

Youcheng Yang

et al.

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: June 8, 2021

Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity. In recent years, reperfusion treatments based on thrombolytic thrombectomy are major managements for ischemic patients, the recanalization time window has been extended to over 24 h. However, extension of window, risk ischemia/reperfusion (I/R) injury following therapy becomes big challenge patient outcomes. I/R leads neuronal death due imbalance in metabolic supply demand, which usually related mitochondrial dysfunction. Mitophagy type selective autophagy referring process specific autophagic elimination damaged or dysfunctional mitochondria prevent generation excessive reactive oxygen species (ROS) subsequent cell death. Recent advances have implicated protective role mitophagy cerebral ischemia mainly associated its neuroprotective effects injury. This review discusses involvement dynamics pathophysiology particular, focusing therapeutic potential regulation possibility using mitophagy-related interventions as an adjunctive approach after stroke.

Language: Английский

Citations

98
ER stress in obesity pathogenesis and management DOI
Amir Ajoolabady, Simin Liu, Daniel J. Klionsky

et al.

Trends in Pharmacological Sciences, Journal Year: 2021, Volume and Issue: 43(2), P. 97 - 109

Published: Dec. 8, 2021

Language: Английский

Citations

83