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The Multiple Roles of Autophagy in Neural Function and Diseases

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neuroscience Bulletin 2024年第3期40卷 363-382页

作者： Yan-Yan Li Zheng-Hong Qin Rui Sheng Department of Pharmacology and laboratory of Aging and Nervous Diseases Jiangsu Key laboratory of Neuropsychiatric DiseasesCollege of Pharmaceutical Sciences of Soochow UniversitySuzhou 215123China

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes,where proteins,lipids,and organelles are degraded and *** to the way the cytoplasmic components are engulfed,autophagy can be divided into macroautophagy,microautophagy,and chaperone-mediated ***,many studies have found that autophagy plays an important role in neurological diseases,including Alzheimer's disease,Parkinson's disease,Huntington's disease,neuronal excitotoxicity,and cerebral *** maintains cell homeostasis in the nervous system via degradation of misfolded proteins,elimination of damaged organelles,and regulation of apoptosis and ***-mTOR,Beclin 1,TP53,endoplasmic reticulum stress,and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological ***,we discuss the role,functions,and signal pathways of autophagy in neurological diseases,which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.

关键词： Autophagy Neurodegenerative diseases Cerebral ischemia AMPK mTOR Beclin 1 TP53 Endoplasmic reticulum stress

Relationship Between Short-chain Fatty Acids and Parkinson’s Disease:A Review from Pathology to Clinic

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neuroscience Bulletin 2024年第4期40卷 500-516页

作者： Wen-Xiang Duan Fen Wang Jun-Yi Liu Chun-Feng Liu Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhou215004China Department of Neurology Dushu Lake Hospital affiliated to Soochow UniversitySuzhou215125China Jiangsu key laboratory of Neuropsychiatric Diseases and Institute of neuroscience Soochow UniversitySuzhou215123China

Parkinson’s disease(PD)is a complicated neurodegenerative disease,characterized by the accumulation ofα-synuclein(α-syn)in Lewy bodies and neurites,and massive loss of midbrain dopamine *** evidence suggests that gut microbiota and microbial metabolites are involved in the development of *** these,short-chain fatty acids(SCFAs),the most abundant microbial metabolites,have been proven to play a key role in brain-gut *** this review,we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor *** research should focus on further elucidating the role of SCFAs in neuroinflammation,as well as developing novel strategies employing SCFAs and their derivatives to treat PD.

关键词： Parkinson’s disease Short-chain fatty acids Microbial metabolites Brain-gut-microbiota axis

Cardiac-Adaptive Conductive Hydrogel Patch Enabling Construction of Mechanical–Electrical Anisotropic Microenvironment for Heart Repair

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Research 2024年第1期2023卷 489-507页

作者： Xiaoping Song Jifeng Zhang Si Shen Dan Liu Jie Zhang Wenming Yin Genlan Ye Leyu Wang Liu Cai Honghao Hou Xiaozhong Qiu Central laboratory The Fifth Affiliated HospitalSouthern Medical UniversityGuangzhouGuangdong 510910China Department of Anatomy Neuroscience Laboratory for Cognitive and Developmental DisordersMedical College of Jinan UniversityGuangzhou 510630China Guangdong Provincial key laboratory of Construction and Detection in Tissue Engineering School of Basic Medical ScienceBiomaterials Research CenterSchool of Biomedical EngineeringSouthern Medical UniversityGuangzhouGuangdong 510515China

The biomimetic construction of a microstructural–mechanical–electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction(MI).Inspired by the 3D anisotropic characteristic of the natural fish swim bladder(FSB),a novel flexible,anisotropic,and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural,conductive,and mechanical features of the native cardiac extracellular *** results revealed that the originally stiff,homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel,enabling its potential as a functional engineered cardiac patch(ECP).In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity,maturation,elongation,and orientation of cardiomyocytes(CMs),and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis,thereby promoting cell retention,myogenesis,and vascularization,as well as improving electrical *** findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.

关键词： bladder thereby patch

Neuronomodulation of Excitable Neurons

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neuroscience Bulletin 2024年第1期40卷 103-112页

作者： Yizhang Chen Lin Xiao Jian Qiu Institute of neuroscience Second Military Medical UniversityShanghai 200433China Institute for Brain Research and Rehabilitation Key Laboratory of BrainCognition and Education Sciences of Ministry of EducationSouth China Normal UniversityGuangzhou 510631China Department of Chemical Physiology and Biochemistry Oregon Health and Science UniversityPortlandOR 97239USA

Neuronomodulation refers to the modulation of neural conduction and synaptic transmission(i.e.,the conduction process involved in synaptic transmission)of excitable neurons via changes in the membrane potential in response to chemical substances,from spillover neuro-transmitters to paracrine or endocrine hormones circulating in the *** can be direct or indirect,depending on the transduction pathways from the ligand binding site to the ion pore,either on the same molecule,*** ion channel,or through an intermediate step on different *** major players in direct neurono-modulation are ligand-gated or voltage-gated ion *** key process of direct neuronomodulation is the binding and chemoactivation of ligand-gated or voltage-gated ion channels,either orthosterically or allosterically,by various *** neuronomodulation involves metabotropic receptor-mediated slow potentials,where steroid hormones,cytokines,and chemokines can implement these *** neuronomodulation is of great significance for understanding the physiological mechanisms of brain function,and the occurrence and treatment of diseases.

关键词： Neuron Membrane potential Excitability Chemoactivation Neuronomodulation

Enhanced Beta2-band Oscillations Denote Auditory Hallucination in Schizophrenia Patients and a Monkey Model of Psychosis

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neuroscience Bulletin 2024年第3期40卷 325-338页

作者： Shuo Ma Tianzhen Chen Wenjun Jia Jie Liu Shihan Ding Puzhe Li Hong Gan Dapeng Zhang Shuxin Shao Mu-Ming Poo Min Zhao Bomin Sun Jian Jiang Department of Neurosurgery Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200020China Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai200030China Shanghai Center for Brain Science and Brain-inspired Technology Lingang LaboratoryShanghai201602China University of California at Berkeley BerkeleyCA94720USA School of Life Science and Technology ShanghaiTech UniversityShanghai201210China Institute of neuroscience CAS Center for Excellence in Brain Science and Intelligence TechnologyCAS Key Laboratory of Primate NeurobiologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai200031China Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology Lingang LaboratoryShanghai201210China Fuyang Third People’s Hospital Fuyang Mental Health CenterFuyang236052China Shanghai key laboratory of Psychotic Disorders Shanghai200030China Institute of Psychological and Behavioral Science Shanghai Jiao Tong UniversityShanghai200030China Shanghai Quanlan Technology Co. LtdShanghai201602China

An electroencephalographic(EEG)signature of auditory hallucinations(AHs)is important for facilitating the diagnosis and treatment of AHs in *** recorded EEG from 25 schizophrenia patients with recurrent *** the period of AHs,EEG recordings exhibited significantly elevated beta2-band power in the temporal region,as compared to those recorded in the absence of AHs or during stimulation with verbal *** further generated methamphetamine-treated rhesus monkeys exhibiting psychosis-like behaviors,including repetitive sudden searching actions in the absence of external intrusion,suggesting the occurrence of *** EEG beta2-band power in the temporal region of these monkeys was enhanced immediately after methamphetamine treatment and positively correlated with the frequency of sudden searching ***,the enhancement of temporal beta2-band oscillations represents a signature for AHs in both patients and a monkey model of psychosis,and this monkey model can be used for developing closed-loop neuromodulation approaches for the treatment of refractory AHs in schizophrenia.

关键词： Schizophrenia Auditory hallucinations Non-human primate Methamphetamine Electroencephalography

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2024年第9期19卷 2081-2088页

作者： Xiaoli Fang Sha Liu Bilal Muhammad Mingxuan Zheng Xing Ge Yan Xu Shu Kan Yang Zhang Yinghua Yu Kuiyang Zheng Deqin Geng Chun-Feng Liu Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Jiangsu key laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Xuzhou Central HospitalXuzhouJiangsu ProvinceChina Jiangsu key laboratory of Neuropsychiatric Disease and Institute of neuroscience Soochow UniversitySuzhouJiangsu ProvinceChina

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal *** dysfunction can precede the onset of motor symptoms by several *** microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain ***/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease *** this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota *** found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor ***,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with ***,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and *** of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier *** results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s ***,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that c

关键词： C/EBP/AEP signaling pathway endotoxemia fecal microbiota transplantation intestinal barrier intestinal inflammation microbiota-gut-brain axis Parkinson’s disease

Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

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Neural Regeneration Research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-Chaves Zainab Maastor Carlos Spuch José Antonio Lamas Lucas C.González-Matías Federico Mallo Biomedical Research Centre(CINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational neuroscience Research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain Biomedical Research Centre(CINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and ***-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain ***-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural *** glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous *** brain insult,microglia are the first cells to respond,followed by reactive *** activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the ***,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many *** processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control *** glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry *** review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkins

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

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Neural Regeneration Research 2024年第9期19卷 2027-2035页

作者： Lulu Xue Ruolan Du Ning Bi Qiuxia Xiao Yifei Sun Ruize Niu Yaxin Tan Li Chen Jia Liu Tinghua Wang Liulin Xiong Transformation Research laboratory The Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina State key laboratory of Biotherapy Sichuan UniversityChengduSichuan ProvinceChina Institute of Neurological Disease Translational Neuroscience CenterWest China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Animal Zoology Institute of NeuroscienceKunming Medical UniversityKunmingYunnan ProvinceChina Department of Anesthesiology The Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina Department of Pediatrics the People’s Liberation Army Rocket Force Characteristic Medical CenterBeijingChina

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic *** therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been ***,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been *** this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor *** chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model *** transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was *** further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering *** found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 ***,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic *** findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

关键词： behavioral evaluations gene knockout human neuroblastoma cells(SH-SY5Y) human placental chorionic derived mesenchymal stem cells interleukin-3 neonatal hypoxic-ischemic encephalopathy nerve injury oxygen-glucose deprivation protein chip small interfering RNA

An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants

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The Innovation 2024年第2期5卷 61-69页

作者： Zhiqiang Duan Yafeng Liang Jialei Sun Hongjin Zheng Tong Lin Pengyu Luo Mengge Wang Ruiheng Liu Ying Chen Shuhua Guo Nannan Jia Hongtao Xie Meili Zhou Minghui Xia Kaijun Zhao Shuhui Wang Na Liu Yongling Jia Wei Si Qitong Chen Yechun Hong Ruilin Tian Jian-Kang Zhu Institute of Advanced Biotechnology and School of Medicine Southern University of Science and TechnologyShenzhen 518055China Bellagen Biotechnology Jinan 250000China Department of Medical neuroscience School of MedicineKey University Laboratory of Metabolism and Health of GuangdongSouthern University of Science and TechnologyShenzhenGuangdong Province 518055China

The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome ***,natural nucleases of this system often exhibit low efficiency,limiting their ***,we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease,*** a result,we developed Cas-SF01,a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian ***-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 *** to natural Cas12i3,Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN *** addition,we identified an amino acid substitution,D876R,that markedly reduced the off-target effect while maintaining high on-target activity,leading to the development of CasSF01^(HiFi)(high-fidelity Cas-SF01).Finally,we show that Cas-SF01 has high gene editing activities in mice and *** results suggest that CasSF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.

关键词： system attractive rational