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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Metabolic reprogramming: a new option for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第4期20卷 1042-1057页

作者： Jiangjie Chen Jinyang Chen Chao Yu Kaishun Xia Biao Yang Ronghao Wang Yi Li Kesi Shi Yuang Zhang Haibin Xu Xuesong Zhang Jingkai Wang Qixin Chen Chengzhen Liang Department of Orthopedics The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Orthopedics Research Institute of Zhejiang university Zhejiang UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province HangzhouZhejiang ProvinceChina Clinical Research Center of Motor System Disease of Zhejiang Province HangzhouZhejiang ProvinceChina Qiandongnan Prefecture People’s hospital KailiGuizhou ProvinceChina Department of Orthopedics Fourth Medical CenterChinese PLA General HospitalBeijingChina

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they *** the ongoing development of various therapies for spinal cord injuries,their effectiveness remains ***,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic *** this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic *** spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic ***,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial *** metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of *** rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell *** available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord *** further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

关键词： axons glycolysis metabolic reprogramming metabolism mitochondria neural regeneration neuroprotection oxidative phosphorylation spinal cord injury therapy

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Unraveling the mechanism of action of Shangxia Liangji formula for treating insomnia:a metabolomics and network pharmacology approach

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Traditional Medicine Research 2025年第2期10卷 16-29页

作者： Xia-Jie Quan Hao Liang Yong-Hong Tang Li Jiang Xiong-Ying Ji Feng-Ying Zhang Ping Zhang Bo Ouyang Department of Information The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Neurology The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Gastroscopy The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Traditional Chinese Medicine The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China

Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of ***,the specific mechanism of action of SXLJF remains ***:The mouse model of insomnia was established by intraperitoneal injection of ***-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive *** open field test and pentobarbital-induced sleeping test were ***-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating ***,key targets were validated using ***:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep *** and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of ***,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,***-qPCR results supported the role of TH in the mechanism of SXLJF in treating ***:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.

关键词： Shangxia Liangji formula insomnia metabolomics network pharmacology tyrosine hydroxylase tyrosine metabolism

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A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

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Neural Regeneration Research 2025年第7期20卷 2029-2037页

作者： Xiao Liang Xingping Quan Xiaorui Geng Yujing Huang Yonghua Zhao Lei Xi Zhen Yuan Ping Wang Bin Liu Faculty of Health sciences University of MacaoMacao Special Administrative RegionChina Center for Cognitive and Brain sciences University of MacaoMacao Special Administrative RegionChina Department of Biomedical Engineering Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina Department of Emergency Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral ***,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly *** this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed *** observed the molding process in mice of different ages and presented age-dependent vascular embolism ***,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a *** imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

关键词： age-dependent cerebral cortex ischemic stroke mouse model optical coherence tomography angiography photoacoustic microscopy photothrombosis vascular imaging

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Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

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Neural Regeneration Research 2025年第8期20卷 2325-2336页

作者： Yafan Bai Hui Ma Yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li Department of Anesthesiology Beijing Tongren HospitalCapital Medical UniversityBeijingChina Beijing Institute of Basic Medical sciences BeijingChina Hebei north university ZhangjiakouHebei ProvinceChina Beijing Institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Key Laboratory of NeuropsychopharmacologyBeijingChina

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary *** this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain *** experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain ***,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 ***,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain ***,YL-0919 effectively combated oxidative stress both in vivo and in *** protective effects of YL-0919 were partially inhibited by *** results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist ***-0919 may have potential as a new treatment for traumatic brain injury.

关键词： antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury

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Single-cell omics: experimental workflow, data analyses and applications

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science china Life sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji university) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life science Chinese Academy of Sciences Peking-Tsinghua Center for Life sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2998-3012页

作者： Yuan Zhao Yidan Zhang Xin Liu Jian Zhang Ya Gao Shuyue Li Cui Chang Xiang Liu Guofeng Yang Department of Geriatrics Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Neurosurgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease *** proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of *** this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s *** a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western *** results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease ***,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control ***,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated *** together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced n

关键词： biomarker diagnosis exosomes N-acetyl-alpha-glucosaminidase Parkinson’s disease proteomic α-synuclein

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Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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Neural Regeneration Research 2025年第8期20卷 2181-2198页

作者： Jiali Chen Yiyang Li Xingping Quan Jinfen Chen Yan Han Li Yang Manfei Zhou Greta Seng Peng Mok Ruibing Wang Yonghua Zhao Institute of Chinese Medical sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmacy Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan ProvinceChina Department of Electrical and Computer Engineering University of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmaceutical sciences Faculty of Health SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on *** vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic ***,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery *** utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly ***,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic *** extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke *** this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification *** the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment ***,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

关键词： delivery engineering extracellular vesicles identification ischemic stroke isolation mitochondria targeting strategy therapeutic effects

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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science china Life sciences 2025年第1期68卷 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer Institute Linzhou Cancer hospital Center for Disease Control and Prevention of Sheyang County Department of Cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan Center for Disease Control and Prevention Office for Cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

关键词： stomach neoplasms precancerous conditions cancer screening cumulative incidence risk stratification

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-Hong Ma Department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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