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Astrocyte in prion disease: a double-edged sword 被引量:1
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作者 Waqas Tahir Simrika Thapa Hermann M.Schatzl 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第8期1659-1665,共7页
Prion diseases are infectious protein misfolding disorders of the central nervous system that result from misfolding of the cellular prion protein(PrPC)into the pathologic isoform PrPSc.Pathologic hallmarks of prion d... Prion diseases are infectious protein misfolding disorders of the central nervous system that result from misfolding of the cellular prion protein(PrPC)into the pathologic isoform PrPSc.Pathologic hallmarks of prion disease are depositions of pathological prion protein PrPSc,neuronal loss,spongiform degeneration and astrogliosis in the brain.Prion diseases affect human and animals,there is no effective therapy,and they invariably remain fatal.For a long time,neuronal loss was considered the sole reason for neurodegeneration in prion pathogenesis,and the contribution of non-neuronal cells like microglia and astrocytes was considered less important.Recent evidence suggests that neurodegeneration during prion pathogenesis is a consequence of a complex interplay between neuronal and non-neuronal cells in the brain,but the exact role of these non-neuronal cells during prion pathology is still elusive.Astrocytes are non-neuronal cells that regulate brain homeostasis under physiological conditions.However,astrocytes can deposit PrPSc aggregates and propagate prions in prion-infected brains.Additionally,sub-populations of reactive astrocytes that include neurotrophic and neurotoxic species have been identified,differentially expressed in the brain during prion infection.Revealing the exact role of astrocytes in prion disease is hampered by the lack of in vitro models of prion-infected astrocytes.Recently,we established a murine astrocyte cell line persistently infected with mouse-adapted prions,and showed how such astrocytes differentially process various prion strains.Considering the complexity of the role of astrocytes in prion pathogenesis,we need more in vitro and in vivo models for exploring the contribution of sub-populations of reactive astrocytes,their differential regulation of signaling cascades,and the interaction with neurons and microglia during prion pathogenesis.This will help to establish novel in vivo models and define new therapeutic targets against prion diseases.In this review,we will discuss the complex role of astrocytes in prion disease,the existing experimental resources,the challenges to analyze the contribution of astrocytes in prion disease pathogenesis,and future strategies to improve the understanding of their role in prion disease. 展开更多
关键词 Alzheimer’s disease ASTROCYTES central nervous system Creutzfeldt-Jakob disease glial cells NEURODEGENERATION prion prion disease prion protein SCRAPIE
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SARM1 participates in axonal degeneration and mitochondrial dysfunction in prion disease
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作者 Meng-Yu Lai Jie Li +10 位作者 Xi-Xi Zhang Wei Wu Zhi-Ping Li Zhi-Xin Sun Meng-Yang Zhao Dong-Ming Yang Dong-Dong Wang Wen Li De-Ming Zhao Xiang-Mei Zhou Li-Feng Yang 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第10期2293-2299,共7页
Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss,axonal degeneration,and mitochondrial dysfunction.Axonal degeneration is an early hallmark ... Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss,axonal degeneration,and mitochondrial dysfunction.Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1.We found that depletion or dysfunctional mutation of SARM1 protected against NAD+loss,axonal degeneration,and mitochondrial functional disorder induced by the neurotoxic peptide PrP106-126.NAD+supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect.NAD+supplementation in PrP106-126-incubated N2a cells,SARM1 depletion,and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival.Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP^(106-126) are partially dependent on SARM1 NADase activity.This pathway has potential as a therapeutic target in the early stages of prion disease. 展开更多
关键词 axonal degeneration mitochondrial dysfunction NAD+metabolism NADase neurodegenerative disease prion disease SARM1 sterile alpha and TIR motif-containing 1
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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds
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作者 Antonio Masone Chiara Zucchelli +2 位作者 Enrico Caruso Giovanna Musco Roberto Chiesa 《Neural Regeneration Research》 SCIE CAS 2025年第4期1009-1014,共6页
PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different patho... PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds. 展开更多
关键词 anti-prion drug anti-PrPC antibody antisense oligonucleotide NEURODEGENERATION pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor
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Epidemiological characteristics of human prion diseases 被引量:8
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作者 Cao Chen Xiao-Ping Dong 《Infectious Diseases of Poverty》 SCIE 2016年第1期394-403,共10页
Human prion diseases are a group of transmissible,progressive,and invariably fatal neurodegenerative disorders,which include Kuru,Creutzfeldt-Jakob disease(CJD),Gerstmann-Sträussler-Scheinker syndrome,and fatal f... Human prion diseases are a group of transmissible,progressive,and invariably fatal neurodegenerative disorders,which include Kuru,Creutzfeldt-Jakob disease(CJD),Gerstmann-Sträussler-Scheinker syndrome,and fatal familial insomnia.Human prion diseases affect approximately 1–2 persons per million worldwide annually,occurring in sporadic,inherited,and acquired forms.These diseases have attracted both scientific and public attention not only because of their mysterious pathogen,but also due to their considerable threat to public health since the emergence of the variant CJD.There are still no specific therapeutic and prophylactic interventions available for prion diseases,thus active surveillance of human prion diseases is critical for disease control and prevention.Since 1993,CJD surveillance systems have been established in many countries and regions,and several long-term multinational cooperative projects have been conducted.In this paper,the epidemiological characteristics of various human prion diseases and the active surveillance systems pertaining to them in different countries and regions are summarized and reviewed. 展开更多
关键词 prion disease EPIDEMIOLOGY Creutzfeldt-Jakob disease SURVEILLANCE
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Genetic Prion Disease:Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease 被引量:3
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作者 Qi Shi Cao Chen +8 位作者 Kang Xiao Wei Zhou Li-Ping Gao Dong-Dong Chen Yue-Zhang Wu Yuan Wang Chao Hu Chen Gao Xiao-Ping Dong 《Neuroscience Bulletin》 SCIE CAS CSCD 2021年第11期1570-1582,共13页
Human genetic prion diseases(gPrDs)are directly associated with mutations and insertions in the PRNP(Prion Protein)gene.We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and J... Human genetic prion diseases(gPrDs)are directly associated with mutations and insertions in the PRNP(Prion Protein)gene.We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020.Nineteen different subtypes were identified and gPrDs accounted for 10.9%of all diagnosed PrDs within the same period.Some subtypes of gPrDs showed a degree of geographic association.The age at onset of Chinese gPrDs peaked in the 50–59 year group.Gerstmann–Sträussler–Scheinker syndrome(GSS)and fatal familial insomnia(FFI)cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease(gCJD)patients with point mutations.A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients.None of the E196A gCJD patients reported a family history.The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD(sCJD).EEG examination was not sensitive for gPrDs.sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients.CSF 14-3-3 positivity was frequently detected in gCJD patients.Increased CSF tau was found in more than half of FFI and T188K gCJD cases,and an even higher proportion of E196A and E200K gCJD patients.63.6%of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC.GSS and FFI cases had longer durations than most subtypes of gCJD.This is one of the largest studies of gPrDs in East Asians,and the illness profile of Chinese gPrDs is clearly distinct.Extremely high proportions of T188K and E196A occur among Chinese gPrDs;these mutations are rarely reported in Caucasians and Japanese. 展开更多
关键词 Genetic prion disease MUTATION SURVEILLANCE Creutzfeldt-Jakob disease Gerstmann-Sträussler-Scheinker syndrome Fatal familial insomnia
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Low activity of complement in the cerebrospinal fluid of the patients with various prion diseases 被引量:1
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作者 Cao Chen Yan Lv +5 位作者 Qi Shi Wei Zhou Kang Xiao Jing Sun Xiao-Dong Yang Xiao-Ping Dong 《Infectious Diseases of Poverty》 SCIE 2016年第1期300-306,共7页
Background:The aim of this study was to analyze the state of activity and levels of complement in the cerebrospinal fluid(CSF)of patients with various prion diseases(PrDs).Findings:The proteomic data emphasized the le... Background:The aim of this study was to analyze the state of activity and levels of complement in the cerebrospinal fluid(CSF)of patients with various prion diseases(PrDs).Findings:The proteomic data emphasized the levels of 20 known complement components found in the CSF of the sCJD panel that were lower than those found in the non-PrD panel.50%of the complement hemolytic activity(CH50)assays revealed significantly lower activity of complement in the CSF of the sCJD panel.The decreased levels of three key complement subunits,C3a/α,C4β,and C9 in the CSF of the sCJD panel were verified by Western blots.Furthermore,the CH50 values in the CSF of 136 sCJD,39 gCJD,22 FFI and 145 non-CJD patients were individually tested.Compared with the control of non-PrD,the CH50 value in the CSF specimens of various PrDs,especially in three subtypes of inherited PrDs,were significantly lower.Relationship analysis identified that the CH50 activity in the CSF was negatively associated with the protein 14–3–3 positive in the CSF.Conclusion:These results indicate a silent complement system in the CSF of PrD patients. 展开更多
关键词 prion diseases CSF Complement component CH50 sCJD
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Therapeutic implications of prion diseases 被引量:1
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作者 Cao Chen Xiaoping Dong 《Biosafety and Health》 CSCD 2021年第2期92-100,共9页
Prions are unconventional infectious agents that cause lethal transmissible neurodegenerative diseases in human and animals.Prions can be distinguished fromother knownpathogens by their lack of nucleic acids.The most ... Prions are unconventional infectious agents that cause lethal transmissible neurodegenerative diseases in human and animals.Prions can be distinguished fromother knownpathogens by their lack of nucleic acids.The most essential process for prion propagation is conversion fromnormal cellular prion protein on the cell membrane to insoluble,limited protease digestion-resistant,pathogenic scrapie prion protein.For dozens of years,many pharmacological tools and interventions targeting different stages of disease progression have been developed and evaluated,and a few have been entered clinical trials.However,no approved prophylactic or therapeutic drugs for prion diseases are available.In this review,we summarize the current concepts in prion research and discuss advances in the research and development of drugs for the prevention and treatment of prion disease. 展开更多
关键词 prion disease Normal cellular prion protein Pathogenic scrapie prion protein IMMUNOTHERAPY Natural extracts
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Protein amplification technology:New advances in human prion disease diagnosis 被引量:1
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作者 Jingxing Wu Dongdong Chen +1 位作者 Qi Shi Xiaoping Dong 《Biosafety and Health》 CSCD 2021年第6期325-332,共8页
Early and accurate diagnosis of human prion diseases is a long-standing difficulty.Currently,the definitive diagnosis of human prion diseases relies on pathognomonic histological features or PrPSc detection of patient... Early and accurate diagnosis of human prion diseases is a long-standing difficulty.Currently,the definitive diagnosis of human prion diseases relies on pathognomonic histological features or PrPSc detection of patients'brain tissue biopsy or autopsy samples,which is not feasible in most cases.Therefore,clinical diagnosis mainly relies on the combinations of the patient’s clinical symptoms.MRI and EEG are used to check for brain damage and detect surrogate markers such as the 14-3-3 protein in Cerebrospinal fluid(CSF),but this is often challenging.In recent years,the development of in vitro cell-free conversion techniques,such as technologies protein misfolding cyclic amplification(PMCA)and real-time quaking-induced conversion(RT-QuIC),have extensively promoted the diagnosis of human prion diseases.PMCA has high diagnostic accuracy in the blood,CSF,and urine samples of variant creutzfeldt–jakob disease(vCJD)patients.Again,RT-QuIC has high diagnostic accuracy for cerebrospinal fluid,olfactory mucosa,and skin samples of sporadic Creutzfeldt Jakob Disease(sCJD)patients.Applying these two technologies is of great significance to the early clinical diagnosis of human prion diseases and the reduction of blood-borne and iatrogenic transmission of prion. 展开更多
关键词 PMCA RT‐QuIC Human prion diseases
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Creutzfeldt-Jakob disease presenting as Korsakoff syndrome caused by E196A mutation in PRNP gene:A case report
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作者 Yong-Kang Zhang Jia-Rui Liu +3 位作者 Kang-Li Yin Yuan Zong Yu-Zhen Wang Ye-Min Cao 《World Journal of Clinical Cases》 SCIE 2023年第25期5982-5987,共6页
BACKGROUND Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations.In humans,prion diseases result from mutations in the prion protein gene(PRNP).Only a... BACKGROUND Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations.In humans,prion diseases result from mutations in the prion protein gene(PRNP).Only a limited number of cases involving a specific PRNP mutation at codon 196(E196A)have been reported.The coexistence of Korsakoff syndrome in patients with Creutzfeldt-Jakob disease(CJD)caused by E196A mutation has not been documented in the existing literature.CASE SUMMARY A 61-year-old Chinese man initially presented with Korsakoff syndrome,followed by rapid-onset dementia,visual hallucinations,akinetic mutism,myoclonus,and hyperthermia.The patient had no significant personal or familial medical history.Magnetic resonance imaging of the brain revealed extensive hyperintense signals in the cortex,while positron emission tomography/computed tomography showed a diffuse reduction in cerebral cortex metabolism.Routine biochemical and microorganism testing of the cerebrospinal fluid(CSF)yielded normal results.Tests for thyroid function,human immunodeficiency virus,syphilis,vitamin B1 and B12 levels,and autoimmune rheumatic disorders were normal.Blood and CSF tests for autoimmune encephalitis and autoantibody-associated paraneoplastic syndrome yielded negative results.A test for 14-3-3 protein in the CSF yielded negative results.Whole-genome sequencing revealed a diseasecausing mutation in PRNP.The patient succumbed to the illness 11 months after the initial symptom onset.CONCLUSION Korsakoff syndrome,typically associated with alcohol intoxication,also manifests in CJD patients.Individuals with CJD along with PRNP E196A mutation may present with Korsakoff syndrome. 展开更多
关键词 prion disease Creutzfeldt-Jakob disease Korsakoff syndrome PRNP gene 14-3-3 proteins Case report
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Peptide aptamer-mediated modulation of prion protein α-cleavage as treatment strategy for prion and other neurodegenerative diseases 被引量:1
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作者 Antonia N.Klein Erica Corda Sabine Gilch 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第12期2108-2110,共3页
Despite intensive research,most neurodegenerative diseases cannot be cured and for some of them no treatment is available to increase survival or quality of life.Among the latter are prion diseases,fatal and transmiss... Despite intensive research,most neurodegenerative diseases cannot be cured and for some of them no treatment is available to increase survival or quality of life.Among the latter are prion diseases,fatal and transmissible neurodegenerative diseases of humans and other animals. 展开更多
关键词 Peptide aptamer-mediated modulation of prion protein cleavage as treatment strategy for prion and other neurodegenerative diseases
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Creutzfeldt Jacob’s Disease: A Senegalese Observation
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作者 Ahmadou Bamba Mbodji Alassane Mamadou Diop +11 位作者 Momo Banda Ndiaye Serigne Saliou Mbacke Khalifa Ababacar Mbaye Rokhaya Diagne Ibrahima Niang Ndiaga Matar Gaye Maouly Fall Adjaratou Sow Anna Basse Lala Bouna Seck Moustapha Ndiaye Amadou Gallo Diop 《Neuroscience & Medicine》 2022年第1期43-48,共6页
Creuzfelt-Jakob Disease is a rare and progressive neurodegenerative disease that results in fatal, transmissible, subacute, spongiform encephalopathy characterized by rapidly progressive dementia and movement disorder... Creuzfelt-Jakob Disease is a rare and progressive neurodegenerative disease that results in fatal, transmissible, subacute, spongiform encephalopathy characterized by rapidly progressive dementia and movement disorder. We present a 62-year-old male with no medical history who was admitted to our hospital because of gait and balance disturbance, language impairment and progressive motor deficit of the four limbs. A neurological examination found frontal lobe syndrome signs, myoclonic movements, pyramidal and extra-pyramidal signs. Brain Magnetic Resonance Imaging detected high intensity areas in the basal ganglia. EEG showed generalized triphasic sharp-wave complexes. A Cerebro Spinal Fluid examination found protein 14-3-3. Death occurred six months after onset. This is the first known case of Creuzfelt-Jakob Disease documented in Senegal. 展开更多
关键词 Creutzfeldt-Jakob disease Protein 14-3-3 prion disease Rapidly Progressive Dementia
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Using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to analyze differentially expressed brain polypeptides in scrapie strain 22L-infected BALB/c mice 被引量:1
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作者 Xiangyu Liao Jiayu Wan +7 位作者 Wensen Liu Xin Tang Wufei Zhu Na XU Jing Xu Nan Li Yaping Chang Chuanjing Ju 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第23期1801-1805,共5页
Differentialiy expressed polypeptides in the brain of a BALB/c mouse model infected with scrapie strain 22L were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results sh... Differentialiy expressed polypeptides in the brain of a BALB/c mouse model infected with scrapie strain 22L were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results showed that 21 peptides were down-regulated, with peptides of mass-to-charge ratio 758.772 5 and mass-to-charge ratio 5 432.206 9, demonstrating the most significant decreases. These finding suggest that these peptides are candidate biomarkers and may play an important role in the pathogenesis of prion disease. 展开更多
关键词 prion diseases misfolded prion protein imaging mass spectrometry PEPTIDES biological markers mass spectrometry
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Preparation of PrP-specific Polyclonal Antibody via Immunization of PRNP-knockout Mice with Recombinant Human PrP Protein 被引量:1
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作者 YANG Xue Hua WU Yue Zhang +4 位作者 XIAO Kang GAO Li Ping CHEN Dong Dong DONG Xiao Ping SHI Qi 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2020年第7期493-501,共9页
Objective The definite diagnosis of human and animal prion diseases depends on the examination of special pathological changes and/or detection of PrPSc in the brain tissues of suspected cases.Thus,developing methods ... Objective The definite diagnosis of human and animal prion diseases depends on the examination of special pathological changes and/or detection of PrPSc in the brain tissues of suspected cases.Thus,developing methods to obtain PrP antibody with good specificity and sensitivity is fundamental for prion identification.Methods We prepared a PrP-specific polyclonal antibody(pAb P54)in a PRNP-knockout mouse model via immunization with recombinant full-length human PrP protein residues 23–231.Thereafter,we verified that pAb in Western blot,immunohistochemistry(IHC),and immunofluorescent(IFA)assays.Results Western blot illustrated that the newly prepared pAb P54 could react with recombinant PrP protein,normal brain PrPC from healthy rodents and humans,and pathological PrPSc in the brains of experimental rodents infected with scrapie and humans infected with different types of prion diseases.The electrophoretic patterns of brain PrPC and PrPSc observed after their reaction with pAb P54 were nearly identical to those produced by commercial PrP monoclonal antibodies.Three glycosylated PrP molecules in the brain homogenates were clearly demonstrated in the reactions of these molecules with pAb P54.IHC assay revealed apparent PrP deposits in the GdnCl-treated brain slices of 139 A-infected mice and 263 K-infected hamsters.IFA tests with pAb P54 also showed clear green signals surrounding blue-stained cell nuclei.Conclusion The newly prepared pAb P54 demonstrated reliable specificity and sensitivity and,thus,may have potential applications not only in studies of prion biology but also in the diagnosis of human and experimental rodent prion diseases. 展开更多
关键词 prion disease PRP ANTIBODY PRNP-knockout mouse
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Seed amplification assay of nasal swab extracts for accurate and non-invasive molecular diagnosis of neurodegenerative diseases
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作者 Suying Duan Jing Yang +9 位作者 Zheqing Cui Jiaqi Li Honglin Zheng Taiqi Zhao Yanpeng Yuan Yutao Liu Lu Zhao Yangyang Wang Haiyang Luo Yuming Xu 《Translational Neurodegeneration》 CSCD 2023年第1期681-690,共10页
Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx.Dysosmia is regarded as an early sign of coronavirus disease 2019(COVID-19),and nasal swab... Nasal swabs are non-invasive testing methods for detecting diseases by collecting samples from the nasal cavity or nasopharynx.Dysosmia is regarded as an early sign of coronavirus disease 2019(COVID-19),and nasal swabs are the gold standard for the detection.By nasal swabs,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)nucleic acids can be cyclically amplified and detected using real-time reverse transcriptase-polymerase chain reaction after sampling.Similarly,olfactory dysfunction precedes the onset of typical clinical manifestations by several years in prion diseases and other neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy.In neurodegenerative diseases,nasal swab tests are currently being explored using seed amplification assay(SAA)of pathogenic misfolded proteins,such as prion,α-synuclein,and tau.These misfolded proteins can serve as templates for the conformational change of other copies from the native form into the same misfolded form in a prion-like manner.SAA for misfolded prion-like proteins from nasal swab extracts has been developed,conceptually analogous to PCR,showing high sensitivity and specificity for molecular diagnosis of degenerative diseases even in the prodromal stage.Cyclic amplification assay of nasal swab extracts is an attractive and feasible method for accurate and non-invasive detection of trace amount of pathogenic substances for screening and diagnosis of neurodegenerative disease. 展开更多
关键词 Nasal swab Seed amplification assay prion disease AMYLOID Neurodegenerative diseases
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Remarkable difference of phospholipid molecular chirality in regulating PrP aggregation and cell responses
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作者 Cunli Wang Xue Wang +7 位作者 Dongdong Wang Shengxu Qian Fusheng Zhang Mingyang Li Minmin Li Wenqi Lu Bo Liu Guangyan Qing 《Chinese Chemical Letters》 SCIE CAS CSCD 2023年第2期236-243,共8页
Prion diseases are fatal neurodegenerative diseases that can cause severe dementia.The misfolding and accumulation of the prion peptide (PrP)_(106–126) is crucial,and this process is closely relevant to biological me... Prion diseases are fatal neurodegenerative diseases that can cause severe dementia.The misfolding and accumulation of the prion peptide (PrP)_(106–126) is crucial,and this process is closely relevant to biological membranes.However,how PrP_(106–126)aggregation is affected by the molecular chirality of phospholipid membrane is unknown.Thus,in this study,a pair of L-and D-aspartic acid (Asp)-modified 1,2-dipalmitoyl-sn–glycero-3-phosphoethanolamine (DPPE) were synthesized to construct chiral liposomes.We discover that L-Asp-DPPE liposomes strongly inhibit the oligomerization and amyloidogenesis of PrP_(106–126),whether acting on monomers or oligomers,which rescues cytotoxicity induced by PrP_(106–126).By comparison,D-Asp-DPPE liposomes inhibit peptide oligomerization only at a high concentration and cannot prevent amyloidogenesis when acting on oligomers,which lead to pronounced cytotoxicity.Apoptosis experiment,dynamic change of intracellular Ca^(2+)(_(i)Ca^(2+)) and Ca^(2+)release from endoplasmic reticulum(ER),reactive oxygen species (ROS) production,adsorption dynamics and affinity tests,and fluorescent imaging clearly disclose that molecular chirality of the liposomes dominates conformational transition of PrP_(106–126)from random coil to β-sheet,binding and adsorption of the monomers and oligomers,and subsequent fibrillation process,resulting in distinct inhibition effect in Ca^(2+)overload and release,ROS production and cell apoptosis.This work is the first to report that interfacial molecular chirality is a potentially crucial influence on the fibrillation process of PrP_(106–126) and its cell responses,whereas the convergence of chiral amino acids and liposomes can be considered potential inhibitors in prion diseases. 展开更多
关键词 prion disease LIPOSOME CHIRALITY Interface Cytosolic Ca^(2+)
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Characteristic analysis of skin keratinocytes in patients with type 2 diabetes based on the single-cell levels 被引量:1
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作者 Bingye Liao Qiuyi Ouyang +4 位作者 Hongqin Song Ziqi Wang Jinhua Ou Jinxin Huang Liang Liu 《Chinese Medical Journal》 SCIE CAS CSCD 2022年第20期2461-2466,共6页
Background: Keratinocytes play an important role in wound healing;however, less is known about skin keratinocytes in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to search for the transcr... Background: Keratinocytes play an important role in wound healing;however, less is known about skin keratinocytes in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to search for the transcriptional characteristics of keratinocytes at the single-cell level from T2DM patients, and to provide experimental data for identifying the pathological mechanisms of keratinocytes under pathological conditions.Methods: We performed single-cell RNA sequencing on the skin tissue from two T2DM patients and one patient without diabetes-induced trauma using the BD Rhapsody^(TM) Single-Cell Analysis System. With the help of bioinformatics R-based single-cell analysis software, we analyzed the results of single-cell sequencing to identify the single-cell subsets and transcriptional characteristics of keratinocytes at the single-cell level, including Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyzes.Results: In this study, we found specific highly expressed signature keratinocyte-related genes. We analyzed the transcriptome of keratinocytes from experimental and control groups and screened a total of 356 differential genes, which were subject to bioinformatics analysis. Enriched pathways included oxidative phosphorylation, antigen processing and presentation, prion and Huntingtons’ diseases, bacterial invasion of epithelial cells, thermogenesis, vasopressin-regulated water reabsorption, and protein processing in the endoplasmic reticulum.Conclusions: This study revealed the characteristics of keratinocytes at the single-cell level and screened a group of differentially expressed genes related to T2DM-associated keratinocytes, oxidative phosphorylation, cytokine receptor interactions, prion diseases, and other signaling pathways. 展开更多
关键词 Diabetes mellitus type 2 Gene Ontology KERATINOCYTES prion diseases Sequence analysis RNA Single-cell analysis TRANSCRIPTOME Wound healing
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