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Natural polyphenols effects on protein aggregates in Alzheimer's and Parkinson's prion-like diseases 被引量:3
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作者 aline freyssin guylène page +1 位作者 bernard fauconneau agnès rioux bilan 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第6期955-961,共7页
Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposit... Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposits are amyloid peptide and tau for Alzheimer's disease, α-synuclein and synphilin-1 for Parkinson's disease. Drugs currently proposed to treat these pathologies do not prevent neurodegenerative processes and are mainly symptomatic therapies. Molecules inducing inhibition of aggregation or disaggregation of these proteins could have beneficial effects, especially if they have other beneficial effects for these diseases. Thus, several natural polyphenols, which have antioxidative, anti-inflammatory and neuroprotective properties, have been largely studied, for their effects on protein aggregates found in these diseases, notably in vitro. In this article, we propose to review the significant papers concerning the role of polyphenols on aggregation and disaggregation of amyloid peptide, tau, α-synuclein, synphilin-1, suggesting that these compounds could be useful in the treatments in Alzheimer's and Parkinson's diseases. 展开更多
关键词 natural polyphenols protein aggregates Alzheimer's disease amyloid peptide amyloid plaques hyperphosphorylated tau Parkinson's disease a-synuclein synphilin-I
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A dual-functional BODIPY-based molecular rotor probe reveals different viscosity of protein aggregates in live cells
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作者 Baoxing Shen Kwan Ho Jung +5 位作者 Songtao Ye Conner A.Hoelzel Charles H.Wolstenholme He Huang Yu Liu Xin Zhang 《Aggregate》 2023年第3期162-168,共7页
Aberrant protein aggregation leads to various human diseases,but little is known about the physical chemical properties of these aggregated proteins in cells.Herein,we developed a boron-dipyrromethene(BODIPY)-based Ha... Aberrant protein aggregation leads to various human diseases,but little is known about the physical chemical properties of these aggregated proteins in cells.Herein,we developed a boron-dipyrromethene(BODIPY)-based HaloTag probe,whose conjugation to HaloTag-fused proteins allows us to study protein aggregates using both fluorescence intensity and lifetime.Modulation of BODIPY fluorophore reveals key structural features to attain the dual function.The optimized probe exhibits increased fluorescence intensity and elongated fluorescence lifetime in protein aggregates.Fluorescence lifetime imaging using this probe indicates that protein aggregates afford different viscosity in the forms of soluble oligomers and insoluble aggregates in live cells.The strategy presented in this work can be extended to enable a wide class of HaloTag probes that can be used to study a variety of physical properties of protein aggregates,thus helping unravel the pathogenic mechanism and develop therapeutic strategy. 展开更多
关键词 fluorescence microscopy fluorescent probes protein aggregates
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Systematic Analysis of Post-Translational Modifications for Increased Longevity of Biotherapeutic Proteins
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作者 Justin Kim Karanveer Sadiora 《Computational Molecular Bioscience》 2024年第3期125-145,共21页
Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and... Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins. 展开更多
关键词 Post-Translational Modification protein-Based Therapeutics Therapeutic Half-Life protein Aggregation protein Reception
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Nucleo-cytoplasmic transport defects and protein aggregates in neurodegeneration 被引量:2
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作者 Giacomo Bitetto Alessio Di Fonzo 《Translational Neurodegeneration》 SCIE CAS 2020年第3期354-369,共16页
In the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates,nucleo-cytoplasmic transport defects have an emerging role.Several pieces of evidenc... In the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates,nucleo-cytoplasmic transport defects have an emerging role.Several pieces of evidence suggest a link between neuronal protein inclusions and nuclear pore complex(NPC)damage.These processes lead to oxidative stress,inefficient transcription,and aberrant DNAVRNA maintenance.The clinical and neuropathological spectrum of NPC defects is broad,ranging from physiological aging to a suite of neurodegenerative diseases.A better understanding of the shared pathways among these conditions may represent a significant step toward dissecting their underlying molecular mechanisms,opening the way to a real possibility of identifying common therapeutic targets. 展开更多
关键词 AGING NEURODEGENERATION Neurodegenerative disease Nucleo-cytoplasmic transport Nuclear pore complex protein aggregate
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RNA binding protein BOULE forms aggregates in mammalian testis
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作者 Yujuan Su Xinghui Guo +3 位作者 Min Zang Zhengyao Xie Tingting Zhao Eugene Yujun Xu 《The Journal of Biomedical Research》 CAS CSCD 2022年第4期255-268,共14页
Amyloids have traditionally been considered pathologic protein aggregates which contribute to neurodegeneration.New evidence however increasingly suggests that non-pathological amyloids are formed in animals during no... Amyloids have traditionally been considered pathologic protein aggregates which contribute to neurodegeneration.New evidence however increasingly suggests that non-pathological amyloids are formed in animals during normal development.Amyloid-like aggregate formation was originally thought to be a conserved feature of animal gametogenesis.This hypothesis was based on findings which suggest that regulated amyloid formations govern yeast meiosis by way of meiosis-specific RNA binding proteins.Additional support came from studies which demonstrate that DAZL,a mammalian gametogenesis-specific RNA binding protein,also forms SDS-resistant aggregates in vivo.Here,we report evidence of aggregated BOULE formations,another DAZ family protein,during sperm development.Data suggest that in mouse testis,BOULE forms SDS-resistant amyloid-like aggregates.BOULE aggregate formation correlates with dynamic developmental expression during spermatogenesis but disappeared in Boule knockout testis.We also mapped essential small region in vitro BOULE aggregations,immediately downstream DAZ repeats,and found that aggregations positively correlated with temperature.We also performed enhanced UV cross-linking immunoprecipitation on BOULE aggregates from mouse testes and found that aggregates bind with a large number of spermatogenesis-related mRNAs.These findings provide insight into the amyloidogenic properties of gametogenesis-specific RNA binding proteins as a conserved feature in mammalian reproduction.Further investigation is warranted to understand the functional significance of BOULE amyloid-like formation during mouse spermatogenesis. 展开更多
关键词 AMYLOID RNA-binding protein BOULE protein aggregation SDD-AGE enhanced UV cross-linking immunoprecipitation
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Ischemic preconditioning induces chaperone hsp70 expression and inhibits protein aggregation in the CA1 neurons of rats 被引量:2
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作者 葛鹏飞 罗天飞 +3 位作者 张纪周 陈大伟 栾永新 付双林 《Neuroscience Bulletin》 SCIE CAS CSCD 2008年第5期288-296,共9页
Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods... Objective To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Methods Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10- min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions. Results Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region (P 〈 0.01 vs 10-min ischemia group). Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates(P〈0.01 vs 10-min ischemia group).Conelusion Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death. 展开更多
关键词 ischemic preconditioning protein aggregation CHAPERONE HSP70
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Consilience and unity in ocular anterior segment research
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作者 Houmam Araj 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第7期1173-1183,共11页
In his beautiful book,Consilience:The Unity of Knowledge,the eminent biologist Edward O Wilson,advocates the need for integration and reconciliation across the sciences.He defines consilience as“literally a‘jumping ... In his beautiful book,Consilience:The Unity of Knowledge,the eminent biologist Edward O Wilson,advocates the need for integration and reconciliation across the sciences.He defines consilience as“literally a‘jumping together’of knowledge with a linking of facts…to create a common groundwork of explanation”.It is the premise of this paper that as much as basic biomedical research is in need of data generation using the latest available techniques–unifying available knowledge is just as critical.This involves the necessity to resolve contradictory findings,reduce silos,and acknowledge complexity.We take the cornea and the lens as case studies of our premise.Specifically,in this perspective,we discuss the conflicting and fragmented information on protein aggregation,oxidative damage,and fibrosis.These are fields of study that are integrally tied to anterior segment research.Our goal is to highlight the vital need for Wilson’s consilience and unity of knowledge which in turn should lead to enhanced rigor and reproducibility,and most importantly,to greater understanding and not simply knowing. 展开更多
关键词 anterior segment ocular surface CORNEA lens CATARACT posterior capsular opacification protein aggregation oxidative damage ANTIOXIDANTS fibrosis wound healing consilience
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Biosensing strategies for amyloid-like protein aggregates
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作者 Yuhang Zhou Shijun Yan +7 位作者 Wanting Dong Chenyao Wu Zhen Zhao Renzhi Wang Yanhong Duo Yongzhi Huang Ding Xu Cheng Jiang 《BMEMat(BioMedical Engineering Materials)》 2024年第1期130-145,共16页
Protein aggregate species play a pivotal role in the pathology of various degenerative diseases.Their dynamic changes are closely correlated with disease progression,making them promising candidates as diagnostic biom... Protein aggregate species play a pivotal role in the pathology of various degenerative diseases.Their dynamic changes are closely correlated with disease progression,making them promising candidates as diagnostic biomarkers.Given the prevalence of degenerative diseases,growing attention is drawn to develop pragmatic and accessible protein aggregate species detection technology.However,the performance of current detection methods is far from satisfying the requirements of extensive clinical use.In this review,we focus on the design strategies,merits,and potential shortcomings of each class of detection methods.The review is organized into three major parts:native protein sensing,seed amplification,and intricate program,which embody three different but interconnected methodologies.To the best of our knowledge,no systematic review has encompassed the entire workflow,from the molecular level to the apparatus organization.This review emphasizes the feasibility of the methods instead of theoretical detection limitations.We conclude that high selectivity does play a pivotal role,while signal compilation,multilateral profiling,and other patient-oriented strategies(i.e.less invasiveness and assay speed)are also important. 展开更多
关键词 biomarker degenerative disease protein aggregates sensor
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Chiral LVFFARK enantioselectively inhibits amyloid-β protein fibrillogenesis 被引量:1
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作者 Wei Liu Xueting Sun +1 位作者 Xiaoyan Dong Yan Sun 《Chinese Journal of Chemical Engineering》 SCIE EI CAS CSCD 2022年第8期227-235,共9页
The modulation of protein aggregation is involved not only in biochemical engineering processes,but also in in vivo biological events such as Alzheimer's disease(AD)that features amyloid-βprotein(Aβ)deposits.Ins... The modulation of protein aggregation is involved not only in biochemical engineering processes,but also in in vivo biological events such as Alzheimer's disease(AD)that features amyloid-βprotein(Aβ)deposits.Inspired by the different pharmacological efficacy of enantiomers,taking heptapeptide LVFFARK(LK7)as an example,herein the chiral influence of peptide inhibitors on Aβfibrillogenesis and cytotoxicity was investigated by extensive biophysical and biological analyses.It was intriguing to find that although both LLK7 and D-LK7 could inhibit Aβaggregation in a concentration-dependent manner,it was the D-enan-tiomer that exhibited chirality preference and selectivity for modulation of Aβself-assembly.As com-pared with L-LK7 at the same conditions,D-LK7 showed significantly enhanced potency on suppressing cross-βsheet formation,fibrillar Aβaggregates deposition,Aβconformational transition,and Aβ-triggered neurotoxicity on cultured cells.For instance,L.LK7 and D-LK7 rescued cells by increasing cell via-bility from 60%to 62%and 84%at 100μmolL^(-1),respectively.The chiral discrimination of L-LK7 and D-LK7 was further validated by the different elimination efficiency on amyloid accumulation in AD model nematodes.It is considered that the higher binding affinity of D-LK7 to Aβmonomers than that of L LK7 resulted in the stronger inhibition effect.This work provided new insights into understanding chiral-ity in the interaction with Aβand the consequent inhibitory effect,and would contribute to the design of anti-amyloid agents. 展开更多
关键词 Alzheimer’s disease Amyloid-b protein protein aggregation CHIRALITY Inhibitor Heptapeptide
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Solution pH jump during antibody and Fc-fusion protein thaw leads to increased aggregation 被引量:1
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作者 Kevin P.Kent Chad E.Schroeder Chandana Sharma 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2018年第5期302-306,共5页
Freeze-thaw cycles impact the amount of aggregation observed in antibodies and Fc-fusion proteins. Various formulation strategies are used to mitigate the amount of aggregation that occurs upon putting a protein solut... Freeze-thaw cycles impact the amount of aggregation observed in antibodies and Fc-fusion proteins. Various formulation strategies are used to mitigate the amount of aggregation that occurs upon putting a protein solution through a freeze-thaw cycle. Additionally, low pH solutions cause native antibodies to unfold, which are prone to aggregate upon pH neutralization, There is great interest in the mechanism that causes therapeutic proteins to aggregate since aggregate species can cause unwanted immunogenicity in patients, Herein, an increase in aggregation is reported when the pH is adjusted from pH 3 up to a pH ranging from pH 4 to pH 7 during the thaw process of a frozen antibody solution, Raising the pH during the thaw process caused a significant increase in the percent aggregation observed. Two antibodies and one Fc-fusion protein were evaluated during the pH jump thaw process and similar effects were observed. The results provide a new tool to study the kinetics of therapeutic protein ag- gregation upon pH increase, 展开更多
关键词 Monoclonal antibodies FREEZE-THAW protein aggregation protein stability
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Insights into Late Embryogenesis Abundant (LEA) Proteins in Plants: From Structure to the Functions 被引量:7
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作者 Imen Amara Ikram Zaidi +4 位作者 Khaled Masmoudi MDolors Ludevid Montserrat Pages Adela Goday Faical Brini 《American Journal of Plant Sciences》 2014年第22期3440-3455,共16页
Late Embryogenesis Abundant (LEA) proteins, a group of hydrophilic proteins, have been linked to survival in plants and animals in periods of stress, putatively through safeguarding enzymatic function and prevention o... Late Embryogenesis Abundant (LEA) proteins, a group of hydrophilic proteins, have been linked to survival in plants and animals in periods of stress, putatively through safeguarding enzymatic function and prevention of aggregation in times of dehydration/heat. Yet despite decades of effort, the molecular-level mechanisms defining this protective function remain unknown. In this paper, we summarize and review research discoveries of the classification of the LEA protein groups based on their amino acid sequence similarity and on the presence of distinctive conserved motifs. Moreover, we focus on high correlation between their accumulation and water deficit, reinforcing their functional relevance under abiotic stresses. We also discuss the biochemical properties of LEA proteins arising from their hydrophilic nature and by amino acid composition. Although significant similarities have not been found between the members of the different groups, a unifying and outstanding feature of most of them is their high hydrophilicity and high content of glycine. Therefore, we have highlighted the biotechnological applications of LEA genes, and the effects of over-expressing LEA genes from all LEA groups from different species of origin into different plant hosts. Apart from agronomical purposes, LEA proteins could be useful for other biotechnological applications in relation to their capacity to prevent aggregation of proteins. 展开更多
关键词 LEA proteins Abiotic Stress protein Aggregation Intrinsically Unstructured proteins(IUPs)
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Pyropia haitanensis polysaccharide extends lifespan by inhibiting protein aggregation in Caenorhabditis elegans
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作者 Zhongshan ZHANG Xiaomei WANG +4 位作者 Yongliang PAN Zhanqi WANG Zhengshun WEN Feng LIU Genxiang MAO 《Journal of Oceanology and Limnology》 SCIE CAS CSCD 2021年第2期705-713,共9页
Pyropia haitanensis polysaccharide(LP)have been found for having many excellent functions such as anti-aging.Using Caenorhabditis elegans models,we evaluated the anti-aging activity of LP by observing the lifespan,rep... Pyropia haitanensis polysaccharide(LP)have been found for having many excellent functions such as anti-aging.Using Caenorhabditis elegans models,we evaluated the anti-aging activity of LP by observing the lifespan,reproduction,pharyngeal pumping,stress response,quantitative fluorescence of polyglutamic acid,and nuclear localization of DAF-16 of worms.The results reveal that LP could extend the adult lifespan of wild-type and polyQ nematodes,indicating a connection of its anti-aging benefit with the toxicity-suppressing effect.The number of polyglutamic acid aggregates in high concentration groups decreased by 24.39%(P<0.05)to the control.The high-dose group strongly induced DAF-16 nuclear translocation over intermediate and cytosolic localizations compared with the control(P<0.001).Therefore,we believe that LP could extend the lifespan and reduce the protein aggregation in C.elegans through nuclear DAF-16∷GFP expression. 展开更多
关键词 Pyropia haitanensis POLYSACCHARIDE protein aggregation Caenorhabditis elegans
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Enhancement of lysosome biogenesis as a potential therapeutic approach for neurodegenerative diseases 被引量:1
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作者 Wenlong Xue Jie Zhang Yang Li 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第11期2370-2376,共7页
Millions of people are suffering from Alzheimer’s disease globally,but there is still no effective treatment for this neurodegenerative disease.Thus,novel therapeutic approaches for Alzheimer’s disease are needed,wh... Millions of people are suffering from Alzheimer’s disease globally,but there is still no effective treatment for this neurodegenerative disease.Thus,novel therapeutic approaches for Alzheimer’s disease are needed,which requires further evaluation of the regulato ry mechanisms of protein aggregate degradation.Lysosomes are crucial degradative organelles that maintain cellular homeostasis.Transcription factor EB-mediated lysosome biogenesis enhances autolysosomedependent degradation,which subsequently alleviates neurodege nerative diseases,including Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease.In this review,we start by describing the key features of lysosomes,including their roles in nutrient sensing and degradation,and their functional impairments in different neurodegenerative diseases.We also explain the mechanisms—especially the post-translational modifications—which impact transcription factor EB and regulate lysosome biogenesis.Next,we discuss strategies for promoting the degradation of toxic protein aggregates.We describe Proteolysis-Ta rgeting Chimera and related technologies for the targeted degradation of specific proteins.We also introduce a group of LYsosome-Enhancing Compounds,which promote transcription factor EB-mediated lysosome biogenesis and improve learning,memory,and cognitive function in APP-PSEN1 mice.In summary,this review highlights the key aspects of lysosome biology,the mechanisms of transcription factor EB activation and lysosome biogenesis,and the promising strategies which are emerging to alleviate the pathogenesis of neurodegenerative diseases. 展开更多
关键词 Alzheimer’s disease degradation lysosome biogenesis LYsosome-Enhancing Compounds neurodegenerative diseases post-translational modifications protein aggregates transcription factor EB
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Protein amyloid aggregate:Structure and function 被引量:1
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作者 Qianhui Xu Yeyang Ma +3 位作者 Yunpeng Sun Dan Li Xin Zhang Cong Liu 《Aggregate》 2023年第4期55-70,共16页
Protein amyloid aggregation has been widely observed to occur and plays impor-tant roles in both physiological processes and pathological diseases.Remarkably,amyloid aggregates assembled by native proteins gain a vari... Protein amyloid aggregation has been widely observed to occur and plays impor-tant roles in both physiological processes and pathological diseases.Remarkably,amyloid aggregates assembled by native proteins gain a variety of different biolog-ical activities,which cannot be adopted by the unassembled protein alone.Thus,it is important to investigate the molecular basis of self-assembly of protein amyloid aggregates and how the aggregated protein structure determines its function.In the review,wefirstly introduce our structural knowledge on how different amyloid pro-teins undergo conformational transition and assemble into amyloid aggregate,with the main focus on amyloidfibril,which is the major species of amyloid aggregate.Then,we elaborate how different structures of amyloidfibrils enable them to fulfill highly diverse functions in either physiological or pathological condition.Further-more,we discuss the structural polymorph which is a very unique feature of amyloidfibril,and its implication in understanding the structure-function relationship of amy-loidfibrils.Finally,we point out the importance of applying and integrating new approaches for deepening the structure-function study of amyloidfibrils and high-light the potential of designing amyloidfibril-based functional bio-nanomaterials for application. 展开更多
关键词 amyloidfibril neurodegenerative diseases prion-like propagation protein phase separation protein aggregate
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One-pot in-situ synthesis of coralloid supported VO_(2)catalyst for intensified aerobic oxidative desulfurization 被引量:2
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作者 Suhang Xun Cancan Wu +5 位作者 Lida Tang Mengmeng Yuan Haofeng Chen Minqiang He Wenshuai Zhu Huaming Li 《Chinese Journal of Chemical Engineering》 SCIE EI CAS CSCD 2023年第4期136-140,共5页
A coralloid 3D g-C_(3)N_(4)supported VO_(2)catalyst was successfully synthesized in-situ by one-pot method,avoiding the agglomeration of VO_(2)during the reaction.The morphological and compositional information of the... A coralloid 3D g-C_(3)N_(4)supported VO_(2)catalyst was successfully synthesized in-situ by one-pot method,avoiding the agglomeration of VO_(2)during the reaction.The morphological and compositional information of the supported catalyst were investigated detailedly.30%VO_(2)/3D g-C_(3)N_(4)revealed excellent catalytic activity in aerobic oxidative desulfurization,the oxidative of dibenzothiophene(DBT),4-methyldibenzothiophene(4-MDBT)and 4,6-dimethyldibenzothiophene(4,6-DMDBT)reached 98.6%,99%and 99.4%,respectively,under the same mild conditions.The recycling performance and the mechanism on the oxidative of DBT were studied as well. 展开更多
关键词 Alzheimer's disease Amyloid-βprotein protein aggregation CHIRALITY Inhibitor Heptapeptide
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α-Synuclein oligomers and fibrils:partners in crime in synucleinopathies 被引量:1
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作者 Alessandra Bigi Roberta Cascella Cristina Cecchi 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第11期2332-2342,共11页
The misfolding and aggregation of a-synuclein is the general hallmark of a group of devastating neurodegenerative pathologies referred to as synucleinopathies,such as Parkinson’s disease,dementia with Lewy bodies,and... The misfolding and aggregation of a-synuclein is the general hallmark of a group of devastating neurodegenerative pathologies referred to as synucleinopathies,such as Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy.In such conditions,a range of different misfolded aggregates,including oligomers,protofibrils,and fibrils,are present both in neurons and glial cells.Growing expe rimental evidence supports the proposition that solu ble oligomeric assemblies,formed during the early phases of the aggregation process,are the major culprits of neuronal toxicity;at the same time,fibrillar confo rmers appear to be the most efficient at propagating among interconnected neurons,thus contributing to the spreading ofα-synuclein pathology.Moreover,α-synuclein fibrils have been recently repo rted to release soluble and highly toxic oligomeric species,responsible for an immediate dysfunction in the recipient neurons.In this review,we discuss the current knowledge about the plethora of mechanisms of cellular dysfunction caused byα-synuclein oligome rs and fibrils,both contributing to neurodegeneration in synucleinopathies. 展开更多
关键词 amyloid aggregation neurodegeneration Parkinson’s disease protein aggregation protein misfolding
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Corrigendum to “Peptide backbone-copper ring structure: A molecular insight into copper-induced amyloid toxicity”
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作者 王静 姜先凯 +9 位作者 苏秀榕 周星飞 王宇 王耿 耿和平 姜政 黄方 陈刚 王春雷 方海平 《Chinese Physics B》 SCIE EI CAS CSCD 2023年第6期716-716,共1页
The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be cr... The author list originally given in Wang et al. Chin. Phys. B 31 108702 (2022) has been amended to remove four authors, Hua Li, Bin Wu, Jun Guo and Chenqi Xu, who believe their contributions are more suitable to be credited in the acknowledgments. 展开更多
关键词 interactions between metal ion and protein quantum chemistry calculation protein aggregation amyloid diseases
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Fluorogenic sensing of amorphous aggregates,amyloid fibers,and chaperone activity via a near-infrared aggregation-induced emission-active probe
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作者 Wei He Yuanyuan Yang +6 位作者 Yuhui Qian Zhuoyi Chen Yongxin Zheng Wenping Zhao Chenxu Yan Zhiqian Guo Shu Quan 《Aggregate》 EI CAS 2024年第1期309-320,共12页
The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these di... The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these disorders.Despite the development of various biosensors and fluorescent probes that selectively target amyloid fibers or amorphous aggregates,there is still a lack of tools capable of simultaneously detecting both types of aggregates.Herein,we demonstrate the quantitative discernment of amorphous aggregates by QM-FN-SO3,an aggregationinduced emission(AIE)probe initially designed for detecting amyloid fibers.This probe easily penetrates the membranes of the widely-used prokaryotic model organism Escherichia coli,enabling the visualization of both amorphous aggregates and amyloid fibers through near-infrared fluorescence.Notably,the probe exhibits sensitivity in distinguishing the varying aggregation propensities of proteins,regardless of whether they form amorphous aggregates or amyloid fibers in vivo.These properties contribute to the successful application of the QM-FN-SO3 probe in the subsequent investigation of the antiaggregation activities of two outer membrane protein(OMP)chaperones,both in vitro and in their physiological environment.Overall,our work introduces a near-infrared fluorescent chemical probe that can quantitatively detect amyloid fibers and amorphous aggregates with high sensitivity in vitro and in vivo.Furthermore,it demonstrates the applicability of the probe in chaperone biology and its potential as a high-throughput screening tool for protein aggregation inhibitors and folding factors. 展开更多
关键词 aggregation-induced emission fluorescence molecular chaperone protein aggregation
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Extracellular quality control in the epididymis 被引量:3
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作者 Gail A. Cornwall H. Henning von Horsten Douglas Swartz Seethal Johnson Kim Chau Sandra Whelly 《Asian Journal of Andrology》 SCIE CAS CSCD 2007年第4期500-507,共8页
The epididymal lumen represents a unique extracellular environment because of the active sperm maturation process that takes place within its confines. Although much focus has been placed on the interaction of epididy... The epididymal lumen represents a unique extracellular environment because of the active sperm maturation process that takes place within its confines. Although much focus has been placed on the interaction of epididymal secretory proteins with spermatozoa in the lumen, very little is known regarding how the complex epididymal milieu as a whole is maintained, including mechanisms to prevent or control proteins that may not stay in their native folded state following secretion. Because some misfolded proteins can form cytotoxic aggregate structures known as amyloid, it is likely that control/surveillance mechanisms exist within the epididymis to protect against this process and allow sperm maturation to occur. To study protein aggregation and to identify extracellular quality control mechanisms in the epididymis, we used the cystatin family of cysteine protease inhibitors, including cystatin-related epididymal spermatogenic and cystatin C as molecular models because both proteins have inherent properties to aggregate and form amyloid. In this chapter, we present a brief summary of protein aggregation by the amyloid pathway based on what is known from other organ systems and describe quality control mechanisms that exist intracellularly to control protein misfolding and aggregation. We then present a summary of our studies of cystatinrelated epididymal spermatogenic (CRES) oligomerization within the epididymal lumen, including studies suggesting that transglutaminase cross-linking may be one mechanism of extracellular quality control within the epididymis. (Asian J Androl 2007 July; 9: 500-507) 展开更多
关键词 EPIDIDYMIS protein aggregation extracellular quality control CYSTATIN TRANSGLUTAMINASE
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One ring is sufficient to inhibit α-synuclein aggregation
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作者 Samuel Peña-Díaz Salvador Ventura 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第3期508-511,共4页
Parkinson's disease,the second most prevalent neurodegenerative disorder worldwide,is characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta,causing motor symptoms.This disor... Parkinson's disease,the second most prevalent neurodegenerative disorder worldwide,is characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta,causing motor symptoms.This disorder's main hallmark is the formation of intraneuronal protein inclusions,named Lewy bodies and neurites.The major component of these arrangements is α-synuclein,an intrinsically disordered and soluble protein that,in pathological conditions,can form toxic and cell-to-cell transmissible amyloid structures.Preventing α-synuclein aggregation has attracted significant effort in the search for a disease-modifying therapy for Parkinson's disease.Small molecules like Synu Clean-D,epigallocatechin gallate,trodusquemine,or anle138 b exemplify this therapeutic potential.Here,we describe a subset of compounds containing a single aromatic ring,like dopamine,ZPDm,gallic acid,or entacapone,which act as molecular chaperones against α-synuclein aggregation.The simplicity of their structures contrasts with the complexity of the aggregation process,yet the block efficiently α-synuclein assembly into amyloid fibrils,in many cases,redirecting the reaction towards the formation of non-toxic off-pathway oligomers.Moreover,some of these compounds can disentangle mature α-synuclein amyloid fibrils.Their simple structures allow structure-activity relationship analysis to elucidate the role of different functional groups in the inhibition of α-synuclein aggregation and fibril dismantling,making them informative lead scaffolds for the rational development of efficient drugs. 展开更多
关键词 amyloid aromatic rings dopamine inhibition NEURODEGENERATION OLIGOMERS Parkinson's disease protein aggregation Α-SYNUCLEIN
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