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Characterization of 10MAG/LDAO reverse micelles: Understanding versatility for protein encapsulation 10MAG/LDAO 反向胶束的表征:了解蛋白质封装的多功能性
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-05-21 DOI: 10.1016/j.bpc.2024.107269
Crystal I. Stackhouse , Kali N. Pierson , Courtney L. Labrecque , Cara Mawson , Joshua Berg , Brian Fuglestad , Nathaniel V. Nucci
{"title":"Characterization of 10MAG/LDAO reverse micelles: Understanding versatility for protein encapsulation","authors":"Crystal I. Stackhouse ,&nbsp;Kali N. Pierson ,&nbsp;Courtney L. Labrecque ,&nbsp;Cara Mawson ,&nbsp;Joshua Berg ,&nbsp;Brian Fuglestad ,&nbsp;Nathaniel V. Nucci","doi":"10.1016/j.bpc.2024.107269","DOIUrl":"10.1016/j.bpc.2024.107269","url":null,"abstract":"<div><p>Reverse micelles (RMs) are spontaneously organizing nanobubbles composed of an organic solvent, surfactants, and an aqueous phase that can encapsulate biological macromolecules for various biophysical studies. Unlike other RM systems, the 1-decanoyl-<em>rac</em>-glycerol (10MAG) and lauryldimethylamine-N-oxide (LDAO) surfactant system has proven to house proteins with higher stability than other RM mixtures with little sensitivity to the water loading (<em>W</em><sub><em>0</em></sub>, defined by the ratio of water to surfactant). We investigated this unique property by encapsulating three model proteins – cytochrome <em>c</em>, myoglobin, and flavodoxin – in 10MAG/LDAO RMs and applying a variety of experimental methods to characterize this system's behavior. We found that this surfactant system differs greatly from the traditional, spherical, monodisperse RM population model. 10MAG/LDAO RMs were discovered to be oblate ellipsoids at all conditions, and as <em>W</em><sub><em>0</em></sub> was increased, surfactants redistributed to form a greater number of increasingly spherical ellipsoidal particles with pools of more bulk-like water. Proteins distinctively influence the thermodynamics of the mixture, encapsulating at their optimal RM size and driving protein-free RM sizes to scale accordingly. These findings inform the future development of similarly malleable encapsulation systems and build a foundation for application of 10MAG/LDAO RMs to analyze biological and chemical processes under nanoscale confinement.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"311 ","pages":"Article 107269"},"PeriodicalIF":3.8,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030146222400098X/pdfft?md5=a46e72d8e11409254904eba31e299c0a&pid=1-s2.0-S030146222400098X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141141422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Critical assessment of popular biomolecular force fields for molecular dynamics simulations of folding and enzymatic activity of main protease of coronavirus SARS-CoV-2 对用于冠状病毒 SARS-CoV-2 主要蛋白酶折叠和酶活性分子动力学模拟的常用生物分子力场进行严格评估
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-05-16 DOI: 10.1016/j.bpc.2024.107258
Kateryna O. Lohachova, Alexander Kyrychenko, Oleg N. Kalugin
{"title":"Critical assessment of popular biomolecular force fields for molecular dynamics simulations of folding and enzymatic activity of main protease of coronavirus SARS-CoV-2","authors":"Kateryna O. Lohachova,&nbsp;Alexander Kyrychenko,&nbsp;Oleg N. Kalugin","doi":"10.1016/j.bpc.2024.107258","DOIUrl":"10.1016/j.bpc.2024.107258","url":null,"abstract":"<div><p>The main cysteine protease (M<sup>pro</sup>) of coronavirus SARS-CoV-2 has become a promising target for computational development in anti-COVID-19 treatments. Here, we benchmarked the performance of six biomolecular molecular dynamics (MD) force fields (OPLS-AA, CHARMM27, CHARMM36, AMBER03, AMBER14SB and GROMOS G54A7) and three water models (TIP3P, TIP4P and SPC) for reproducing the native fold and the enzymatic activity of M<sup>pro</sup> as monomeric and dimeric units. The MD sampling up to 1 μs suggested that the proper choice of the force fields and water models plays an essential role in reproducing the tertiary structure and the inter-residue distance between the catalytic dyad His41-Cys145. We found that while most benchmarked all-atom force fields reproduce well the native fold of M<sup>pro</sup>, the CHARMM27/TIP3P and OPLS-AA/TIP4P setups revealed a good performance in reproducing the structure of the catalytic domain. In addition, these FF setups were also well-adopted for MD sampling of M<sup>pro</sup> at the physiologic conditions by mimicking the presence of 100 mM NaCl and the elevated temperature of 310 K. Finally, both FFs were also performed well in reproducing the native fold of M<sup>pro</sup> in a dimeric form. Therefore, comparing the preservation of the native fold of M<sup>pro</sup> and the stability of its catalytic site architecture, our MD benchmarking suggests that the OPLS-AA/TIP4P and CHARMM27/TIP3P MD setups at the physiologic conditions may be well-suited for rapid <em>in silico</em> screening and developing broad-spectrum anti-coronaviral therapeutic agents.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"311 ","pages":"Article 107258"},"PeriodicalIF":3.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141030732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling the characteristics of D4 and R4 aptamers for their future use in prostate cancer clinical practice 揭示D4和R4适配体的特性,促进其在前列腺癌临床实践中的应用
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-05-14 DOI: 10.1016/j.bpc.2024.107259
Esther Campos-Fernández, Nathalia Oliveira Alqualo, Emília Rezende Vaz, Cláudia Mendonça Rodrigues, Vivian Alonso-Goulart
{"title":"Unveiling the characteristics of D4 and R4 aptamers for their future use in prostate cancer clinical practice","authors":"Esther Campos-Fernández,&nbsp;Nathalia Oliveira Alqualo,&nbsp;Emília Rezende Vaz,&nbsp;Cláudia Mendonça Rodrigues,&nbsp;Vivian Alonso-Goulart","doi":"10.1016/j.bpc.2024.107259","DOIUrl":"10.1016/j.bpc.2024.107259","url":null,"abstract":"<div><p>The DNA and RNA aptamers D4 and R4, respectively, emerged from the modification of PC-3 cell-binding aptamer A4. Our objective was to characterize the aptamers <em>in silico</em> and <em>in vitro</em> and begin to identify their target molecules. We represented their structures using computational algorithms; evaluated their binding to several prostate cell lines and their effects on the viability and migration of these cells; and determined their dissociation constant by flow cytometry. We analyzed circulating prostate tumor cells from patients using D4, R4, anti-CD133 and anti-CD44. Finally, the target proteins of both aptamers were precipitated and identified by mass spectrometry to simulate their <em>in silico</em> docking. The aptamers presented similar structures and bound to prostate tumor cells without modifying the cellular parameters studied, but with different affinities. The ligand cells for both aptamers were CD44<sup>+</sup>, indicating that they could identify cells in the mesenchymal stage of the metastatic process. The possible target proteins NXPE1, ADAM30, and MUC6 need to be further studied to better understand their interaction with the aptamers. These results support the development of new assays to determine the clinical applications of D4 and R4 aptamers in prostate cancer.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"311 ","pages":"Article 107259"},"PeriodicalIF":3.8,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141055383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating the role of axonal ion channel cooperativity in action potential dynamics: Studies on Hodgkin-Huxley's model 研究轴突离子通道合作性在动作电位动力学中的作用:霍奇金-赫胥黎模型研究
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-05-08 DOI: 10.1016/j.bpc.2024.107257
Jitender Kumar , Patrick Das Gupta , Subhendu Ghosh
{"title":"Investigating the role of axonal ion channel cooperativity in action potential dynamics: Studies on Hodgkin-Huxley's model","authors":"Jitender Kumar ,&nbsp;Patrick Das Gupta ,&nbsp;Subhendu Ghosh","doi":"10.1016/j.bpc.2024.107257","DOIUrl":"10.1016/j.bpc.2024.107257","url":null,"abstract":"<div><p>Voltage-gated ion channels play an important role in generating action potential in neurons. These ion channels are found to be in localized cluster form on the axonal membrane surface and behave cooperatively. However, in Hodgkin &amp; Huxley's model of action potential the ion channels are considered to function independently. According to some recent reports, the activity of an ion channel is influenced by the neighboring ion channels' activities. We have modified the Hodgkin-Huxley's model based on our previous studies on cooperativity among ion channels. Computational analysis of the proposed model shows that the initiation of the action potential, amplitude and hyperpolarization are affected significantly by the cooperative interactions among the voltage-gated ion channels present on the axonal membrane surface. These results are qualitatively supported by the existing experimental facts.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"311 ","pages":"Article 107257"},"PeriodicalIF":3.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141054388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Improved analysis of NMR chemical shift perturbations through an error estimation method 通过误差估算方法改进核磁共振化学位移扰动分析
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-05-06 DOI: 10.1016/j.bpc.2024.107255
Kyoko Furuita , Chojiro Kojima
{"title":"Improved analysis of NMR chemical shift perturbations through an error estimation method","authors":"Kyoko Furuita ,&nbsp;Chojiro Kojima","doi":"10.1016/j.bpc.2024.107255","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107255","url":null,"abstract":"<div><p>In solution NMR, chemical shift perturbation (CSP) experiments are widely employed to study intermolecular interactions. However, excluding the nonsignificant peak shift is difficult because little is known about errors in CSP. Here, to address this issue, we introduce a method for estimating errors in CSP based on the noise level. First, we developed a technique that involves line shape fitting to estimate errors in peak position via Monte Carlo simulations. Second, this technique was applied to estimate errors in CSP. In intermolecular interaction analysis of VAP-A with SNX2, error estimation of CSP enabled the evaluation of small but significant changes in peak position and yielded detailed insights that are unattainable with conventional CSP analysis. Third, this technique was successfully applied to estimate errors in residual dipolar couplings. In conclusion, our error estimation method improves CSP analysis by excluding the nonsignificant peak shift.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"310 ","pages":"Article 107255"},"PeriodicalIF":3.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the physicochemical properties of the integration of Tristearoyl uridine in Langmuir monolayers: An approach to cell membrane modeling for prodrugs 探索三苯甲酰基尿苷在朗缪尔单层中整合的物理化学特性:原药细胞膜建模方法
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-05-06 DOI: 10.1016/j.bpc.2024.107256
Felipe Almeida Moreira , Jhon Fernando Berrío Escobar , Cristiano Giordani , Luciano Caseli
{"title":"Exploring the physicochemical properties of the integration of Tristearoyl uridine in Langmuir monolayers: An approach to cell membrane modeling for prodrugs","authors":"Felipe Almeida Moreira ,&nbsp;Jhon Fernando Berrío Escobar ,&nbsp;Cristiano Giordani ,&nbsp;Luciano Caseli","doi":"10.1016/j.bpc.2024.107256","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107256","url":null,"abstract":"<div><p>Understanding the mechanisms by which drugs interact with cell membranes is crucial for unraveling the underlying biochemical and biophysical processes that occur on the surface of these membranes. Our research focused on studying the interaction between an ester-type derivative of tristearoyl uridine and model cell membranes composed of lipid monolayers at the air-water interface. For that, we selected a specific lipid to simulate nontumorigenic cell membranes, namely 1,2-dihexadecanoyl-<em>sn</em>-glycero-3-phospho-<span>l</span>-serine. We noted significant changes in the surface pressure-area isotherms, with a noticeable shift towards larger areas, which was lower than expected for ideal mixtures, indicating monolayer condensation. Furthermore, the viscoelastic properties of the interfacial film demonstrated an increase in both the elastic and viscous parameters for the mixed film. We also observed structural alterations using vibrational spectroscopy, which revealed an increase in the all-trans to gauche conformers ratio. This confirmed the stiffening effect of the prodrug on the lipid monolayer. In summary, this study indicates that this lipophilic prodrug significantly impacts the lipid monolayer's thermodynamic, rheological, electrical, and molecular characteristics. This information is crucial for understanding how the drug interacts with specific sites on the cellular membrane. It also has implications for drug delivery, as the drug's passage into the cytosol may involve traversing the lipid bilayer.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"310 ","pages":"Article 107256"},"PeriodicalIF":3.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-resolution heteronuclear correlations between spin-1/2 and half-integer quadrupolar nuclei under fast MAS solid-state NMR 快速 MAS 固态 NMR 下自旋-1/2 和半整数四极核之间的高分辨率异核相关性
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-05-03 DOI: 10.1016/j.bpc.2024.107254
Manoj Kumar Pandey , Yusuke Nishiyama
{"title":"High-resolution heteronuclear correlations between spin-1/2 and half-integer quadrupolar nuclei under fast MAS solid-state NMR","authors":"Manoj Kumar Pandey ,&nbsp;Yusuke Nishiyama","doi":"10.1016/j.bpc.2024.107254","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107254","url":null,"abstract":"<div><p>High isotropic resolution is essential for the structural elucidation of samples with multiple sites. In this study, utilizing the benefits of TRAPDOR-based heteronuclear multiple quantum coherence (T-HMQC) and a pair of one rotor period long cosine amplitude modulated low-power (cos-lp) pulse-based symmetric-split-<em>t</em><sub>1</sub> multiple-quantum magic angle spinning (MQMAS) methods, we have developed a proton-detected 2D <sup>35</sup>Cl/<sup>1</sup>H T-HMQC-MQMAS pulse sequence under fast MAS (70 kHz) to achieve high-resolution in the indirect dimension of the spin-3/2 (<sup>35</sup>Cl) nuclei connected via protons. As T-HMQC polarizes not only single-quantum central transition (SQ<sub>CT</sub>) but also triple-quantum (TQ) coherences, the proposed 2D pulse sequence is implemented via selection of two coherence pathways (SQ<sub>CT</sub> <span><math><mo>→</mo></math></span>TQ <span><math><mo>→</mo></math></span>SQ<sub>CT</sub> and TQ <span><math><mo>→</mo></math></span> SQ<sub>CT</sub> <span><math><mo>→</mo></math></span>TQ) resulting in the <sup>35</sup>Cl isotropic dimension and is superior to the existing double-quantum satellite-transition (DQ<sub>ST</sub>) T-HMQC in terms of resolution.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"310 ","pages":"Article 107254"},"PeriodicalIF":3.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A benchmark for evaluation of structure-based online tools for antibody-antigen binding affinity 基于结构的抗体-抗原结合亲和力在线工具评估基准
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-04-30 DOI: 10.1016/j.bpc.2024.107253
Jiayi Xu , Jianting Gong , Xiaochen Bo , Yigang Tong , Zilin Ren , Ming Ni
{"title":"A benchmark for evaluation of structure-based online tools for antibody-antigen binding affinity","authors":"Jiayi Xu ,&nbsp;Jianting Gong ,&nbsp;Xiaochen Bo ,&nbsp;Yigang Tong ,&nbsp;Zilin Ren ,&nbsp;Ming Ni","doi":"10.1016/j.bpc.2024.107253","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107253","url":null,"abstract":"<div><p>The prediction of binding affinity changes caused by missense mutations can elucidate antigen-antibody interactions. A few accessible structure-based online computational tools have been proposed. However, selecting suitable software for particular research is challenging, especially research on the SARS-CoV-2 spike protein with antibodies. Therefore, benchmarking of the mutation-diverse SARS-CoV-2 datasets is critical. Here, we collected the datasets including 1216 variants about the changes in binding affinity of antigens from 22 complexes for SARS-CoV-2 S proteins and 22 monoclonal antibodies as well as applied them to evaluate the performance of seven binding affinity prediction tools. The tested tools' Pearson correlations between predicted and measured changes in binding affinity were between −0.158 and 0.657, while accuracy in classification tasks on predicting increasing or decreasing affinity ranged from 0.444 to 0.834. These tools performed relatively better on predicting single mutations, especially at epitope sites, whereas poor performance on extremely decreasing affinity. The tested tools were relatively insensitive to the experimental techniques used to obtain structures of complexes. In summary, we constructed a list of datasets and evaluated a range of structure-based online prediction tools that will explicate relevant processes of antigen-antibody interactions and enhance the computational design of therapeutic monoclonal antibodies.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"311 ","pages":"Article 107253"},"PeriodicalIF":3.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141068645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Self-assembly of spin-labeled antimicrobial peptides magainin 2 and PGLa in lipid bilayers 自旋标记的抗菌肽 magainin 2 和 PGLa 在脂质双层膜中的自组装
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-04-22 DOI: 10.1016/j.bpc.2024.107251
Victoria N. Syryamina , Christopher Aisenbrey , Maria Kardash , Sergei A. Dzuba , Burkhard Bechinger
{"title":"Self-assembly of spin-labeled antimicrobial peptides magainin 2 and PGLa in lipid bilayers","authors":"Victoria N. Syryamina ,&nbsp;Christopher Aisenbrey ,&nbsp;Maria Kardash ,&nbsp;Sergei A. Dzuba ,&nbsp;Burkhard Bechinger","doi":"10.1016/j.bpc.2024.107251","DOIUrl":"10.1016/j.bpc.2024.107251","url":null,"abstract":"<div><p>The cationic antimicrobial peptides PGLa and magainin 2 (Mag2) are known for their antimicrobial activity and synergistic enhancement in antimicrobial and membrane leakage assays. Further use of peptides in combinatory therapy requires knowledge of the mechanisms of action of both individual peptides and their mixtures. Here, electron paramagnetic resonance (EPR), double electron-electron resonance (DEER, also known as PELDOR) and electron spin echo envelope modulation (ESEEM) spectroscopies were applied to study self-assembly and localization of spin-labeled PGLa and Mag2 in POPE/POPG membranes with a wide range of peptide/lipid ratios (P/L) from ∼1/1500 to 1/50. EPR and DEER data showed that both peptides tend to organize in clusters, which occurs already at the lowest peptide/lipid molar ratio of 1/1500 (0.067 mol%). For individual peptides, these clusters are quite dense with intermolecular distances of the order of ∼2 nm. In the presence of a synergistic peptide partner, these homo-clusters are transformed into lipid-diluted hetero-clusters. These clusters are characterized by a local surface density that is several times higher than expected from a random distribution. ESEEM data indicate a slightly different insertion depth of peptides in hetero-clusters when compared to homo-clusters.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"310 ","pages":"Article 107251"},"PeriodicalIF":3.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301462224000802/pdfft?md5=978c2d3eff98400fc4cd7684e01656f1&pid=1-s2.0-S0301462224000802-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140795515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis 淀粉样蛋白形成的胰淀粉样蛋白诱发的神经炎症:机理假说的依据
IF 3.8 3区 生物学
Biophysical chemistry Pub Date : 2024-04-22 DOI: 10.1016/j.bpc.2024.107252
Noah S. Leibold, Florin Despa
{"title":"Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis","authors":"Noah S. Leibold,&nbsp;Florin Despa","doi":"10.1016/j.bpc.2024.107252","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107252","url":null,"abstract":"<div><p>Amylin is a systemic neuroendocrine hormone co-expressed and co-secreted with insulin by pancreatic β-cells. In persons with thype-2 diabetes, amylin forms pancreatic amyloid triggering inflammasome and interleukin-1β signaling and inducing β-cell apoptosis. Here, we summarize recent progress in understanding the potential link between amyloid-forming pancreatic amylin and Alzheimer's disease (AD). Clinical data describing amylin pathology in AD alongside mechanistic studies in animals are reviewed. Data from multiple research teams indicate higher amylin concentrations are associated with increased frequency of cognitive impairment and amylin co-aggregates with β-amyloid in AD-type dementia. Evidence from rodent models further suggests cerebrovascular amylin accumulation as a causative factor underlying neurological deficits. Analysis of relevant literature suggests that modulating the amylin-interleukin-1β pathway may provide an approach for counteracting neuroinflammation in AD.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"310 ","pages":"Article 107252"},"PeriodicalIF":3.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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