Disease-related Peptides Research Articles

Efficient inhibition of amyloid fibrillation and cytotoxicity of α-synuclein and human insulin using biosynthesized silver nanoparticles decorated by green tea polyphenols

Green tea polyphenols (GTPs), particularly epigallocatechin-3-gallate, stand out among natural small molecules screened for their ability to target protein aggregates due to their potent anti-amyloidogenic and neuroprotective activities against various disease-related peptides and proteins. However, the clinical applications of GTPs in amyloid-related diseases have been greatly limited by drawbacks such as poor chemical stability and low bioavailability. To address these limitations, this study utilized an Iranian green tea polyphenolic extract as a reducing agent to neutralize silver ions and facilitate the formation of silver nanoparticle capped by GTPs (GTPs-capped AgNPs). The results obtained from this study demonstrate that GTPs-capped AgNPs are more effective than free GTPs at inhibiting amyloid fibrillation and reducing cytotoxicity induced by amyloid fibrils of human insulin and α-synuclein (α-syn). This improved efficacy is attributed to the increased surface/volume ratio of GTPs-capped AgNPs, which can enhance their binding affinity to amyloidogenic species and boosts their antioxidant activity. The mechanism by which GTPs-capped AgNPs inhibit amyloid fibrillation appears to vary depending on the target protein. For structured protein human insulin, GTPs-capped AgNPs hinder fibrillation by constraining the protein in its native-like state. In contrast, GTPs-capped AgNPs modulate fibrillation of intrinsically disordered proteins like α-syn by redirecting the aggregation pathway towards the formation of non-toxic off-pathway oligomers or amorphous aggregates. These findings highlight polyphenol-functionalized nanoparticles as a promising strategy for targeting protein aggregates associated with neurodegenerative diseases.

274. Potential HIV vaccine gp41 epitope targeting antibodies identify peptides with similarity to proposed Kawasaki disease related peptide, suggesting non-specific mimotope targeting of acidic amino acid enriched regions

Abstract Background We have previously isolated a highly mutated (83% homologous to predicted heavy chain germline) antibody (Ab) termed C group 76-Q13-6F5 (6F5) that targets a conformational epitope on gp41. 6F5, though non-neutralizing, has the capacity to mediate Ab dependent cell cytotoxicity (ADCC). When the variable chain (predicted to be VH1-02 derived) was mutated to germline (termed C group 76 ancestor, or 76Canc), surprisingly this Ab still exhibited significant ADCC activity. Many HIV vaccine strategies are focused on raising highly mutated Abs. We propose that there would be an advantage to developing vaccines related to epitopes that permit functional targeting by Abs using germline variable gene sequences. Methods To explore potential protein targets for vaccination strategies to raise and develop such Abs, we interrogated a peptide array of 29,127 linear peptides using PEPperCHIP® Human Epitome Microarray. We then confirmed peptide binding by Western blot and ELISAs. We also assessed binding to CDI laboratories HuProt protein microarray, containing > 21,000 human proteins. Results 76Canc specifically recognized a number of peptides enriched for glutamic and aspartic acid residues (top hit DEEEEYDEDEYEYDE). Meme analysis of positive peptides revealed a peptide sequence most similar to Hepatitis C virus, similar to a peptide implicated in Kawasaki disease (KD). We confirmed specific binding of four of the top peptide hits, including hepatitis C peptide recognition. We then confirmed binding of 76Canc-related Abs to a published optimized KD related peptide (KPAVIPDREALYQDIDEMEEC). Serum from KD and infectious controls was used to compete with biotinylated 76Canc-related Abs. Serum Abs targeting this epitope showed no specific correlation to having KD. Autoantigen screening of 76Canc identified a single human protein of interest that did contain acidic amino acid rich regions.Figure 1:HIV-1 gp41 antibodies recognize peptides similar to peptide implicated in Kawasaki Disease Conclusion This study reveals acidic motif targeting by specific anti-gp41 Abs and the derived germline Ab, but no evidence that these Abs are related to inflammation similar to KD. Cautious development of targeting such Abs by vaccination is warranted. Future structural comparison of these peptides with native proteins and binding competition studies are needed to confirm mimotope binding. Disclosures Mark D. Hicar, MD/PhD, Pfizer: site investigator for 2 trial

Single-molecule FRET imaging and deep learning reveal concentration dependence of aggregation pathways during Aβ aggregation.

Protein aggregation into amyloid fibrils is the hallmark of several devasting neurodegenerative diseases. Gaining an understanding of disease etiology hinges on our ability to understand the molecular mechanics of how soluble monomers assemble to form insoluble fibrils consisting of thousands of constituent monomers. Although amyloid fibril formation is a highly specific self-assembly process, growth patterns and resultant fibril morphologies are highly dependent on solution conditions. Using fluorescence lifetime imaging and deep learning, we have recently shown that amyloid assembly occurs via heterogeneous aggregation pathways resulting in a mixture of co-present mature fibrils with unique morphologies and physicochemical properties (Meng et al., PNAS_2022_e2116736119). Bulk biophysical methods are unable to fully characterize these mixtures of fibril polymorphs. Here, we further develop and use Förster resonance energy transfer (FRET) imaging to monitor the entire aggregation pathway of the Alzheimer's Disease related peptide amyloid β 42 (Aβ42) at the single fibril level in real time. We incubated a mixture of donor-labeled, acceptor-labeled, and unlabeled Aβ42 monomers, which resulted in the formation of fibrils with diverse FRET efficiency values, indicating structural heterogeneity. Single-fibril images reveal that increasing monomer concentration promotes the formation of more homogeneous fibrils. Fibrils formed at lower concentrations show assemble via highly heterogeneous pathways. Deep learning methods (https://github.com/hoisunglab/FNet) enable segmentation of single fibrils within images of highly overlapping fibrils, allowing for quantitative analysis of the aggregation process in terms of fibril growth rate and photon density for each fibril over the course of fibril assembly.

Identification of Single Amino Acid Chiral and Positional Isomers Using an Electrostatically Asymmetric Nanopore.

Chirality is essential in nearly all biological organizations and chemical reactions but is rarely considered due to technical limitations in identifying L/D isomerization. Using OmpF, a membrane channel from Escherichia coli with an electrostatically asymmetric constriction zone, allows discriminating chiral amino acids in a single peptide. The heterogeneous distribution of charged residues in OmpF causes a strong lateral electrostatic field at the constriction. This laterally asymmetric constriction zone forces the sidechains of the peptides to specific orientations within OmpF, causing distinct ionic current fluctuations. Using statistical analysis of the respective ionic current variations allows distinguishing the presence and position of a single amino acid with different chiralities. To explore potential applications, the disease-related peptide β-Amyloid and its d-Asp1 isoform and a mixture of the icatibant peptide drug (HOE 140) and its d-Ser7 mutant have been discriminated. Both chiral isomers were not applicable to be distinguished by mass spectroscopy approaches. These findings highlight a novel sensing mechanism for identifying single amino acids in single peptides and even for achieving single-molecule protein sequencing.

Aggregation of a Parkinson's Disease-Related Peptide: When Does Urea Weaken Hydrophobic Interactions?

While the exact cause of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease is not completely understood, compelling evidence implicates the aggregation of specific proteins and peptides. Co-solvents can provide molecular insight into protein aggregation mechanisms and the chemical nature of potential aggregation inhibitors. Here, we study, through molecular simulations, the hydration and binding free energies of an amphiphilic peptide from the nonamyloid-β component (NAC), a key aggregation-prone domain of α-synuclein, in water and an 8 M aqueous urea solution. Isoleucine, glycine, and serine peptides of the same length are also studied to unravel the role of urea in the hydration and aggregation of hydrophobic and hydrophilic domains. A strong impact of urea in hindering the aggregation of the NAC subdomain is observed. A slightly weaker aggregation inhibition is observed for the Gly and Ser peptides, whereas a much lower aggregation inhibitory activity is found for the Ile peptide, seemingly contrasting with urea's protein unfolding mechanism. This behavior is shown to derive from a lower profusion of urea next to the hydrophobic side chains and the backbone of the Ile's peptide in the dimeric form. As a consequence, β-sheets, formed upon aggregation, remain nearly intact. Hydrophilic neighbor groups in the amphiphilic NAC subdomain, however, are shown to anchor enough urea to weaken hydrophobic interactions and disrupt β-sheet structures. Our results indicate that urea's activity is potentiated in amphiphilic domains and that potential drugs could disrupt hydrophobic β-sheet-rich regions while not binding primarily to hydrophobic amino acids.

Development of a Hybrid-Resolution Force Field for Peptide Self-Assembly Simulations: Optimizing Peptide-Peptide and Peptide-Solvent Interactions.

Atomic descriptions of peptide self-assembly are crucial to an understanding of disease-related peptide aggregation and the design of peptide-assembled materials. Obtaining these descriptions through computer simulation is challenging because current force fields, which were not designed for this process and are often unable to describe correctly peptide self-assembly behavior and the sequence dependence. Here, we developed a framework using dipeptide aggregation as a model system to improve force fields for simulations of self-assembly. Aggregation-related structural properties were designed and used to guide the optimization of peptide-peptide and peptide-solvent interactions. With this framework, we developed a self-assembly force field, termed PACE-ASM, by reoptimizing a hybrid-resolution force field that was originally developed for folding simulation. With its applicability in folding simulations, the new PACE was used to simulate the self-assembly of two disease-related short peptides, Aβ16-21 and PHF6, into β-sheet-rich cross-β amyloids. These simulations reproduced the crystal structures of Aβ16-21 and PHF6 amyloids at near-atomic resolution and captured the difference in packing orientations between the two sequences, a task which is challenging even with all-atom force fields. Apart from cross-β amyloids, the self-assembly of emerging helix-rich cross-α amyloids by another peptide PSMα3 can also be correctly described with the new PACE, manifesting the versatility of the force field. We demonstrated that the ability of the PACE-ASM to model peptide self-assembly is based largely on its improved description of peptide-peptide and peptide-solvent interactions. This was achieved with our optimization framework that can readily identify and address the deficiency in describing these interactions.

ACHP: A Web Server for Predicting Anti-Cancer Peptide and Anti-Hypertensive Peptide

Peptide drugs are generally compounds with 2–50 amino acids connected by peptide bonds and having drug effects. Because of their unique advantages such as significant activity, strong specificity, and low toxicity, some of them are applied in the treatment of various diseases. The design and development of new peptide drugs have broad prospects, and determining the molecular characteristics of disease-related peptide drugs is the key to drug design. This research takes anti-cancer peptides and anti-hypertensive peptides as the research objects, and we propose a novel method of describing peptide drugs, making use of the topological attribute values in an amino acid interaction network to represent the characteristics of peptides. In addition, peptide drugs are described from different perspectives by combining the information of the primary, secondary and tertiary structures. Three algorithms including support vector machine (SVM), K-nearest neighbor (KNN) and random forest (RF) are utilized to train the model. Then the support vector machine based on recursive feature elimination method (SVM-RFE) removes redundant features and identifies the key characteristics of different types of drugs. The added network features can more comprehensively describe peptide drugs, providing a theoretical basis for the analysis and design of new peptide drugs. The web sever of ACHP is freely available at http://118.178.58.31:9801/ .

Fast Purification of Recombinant Monomeric Amyloid-β from E. coli and Amyloid-β-mCherry Aggregates from Mammalian Cells.

The Alzheimer’s disease related peptide, Amyloid-beta (Aβ)1–40 and 1–42, has proven difficult to be purified as a recombinant monomeric protein due its expression in E. coli leading to the formation of insoluble inclusion bodies and its tendency to quickly form insoluble aggregates. A vast array of methods have been used so far, yet many have pitfalls, such as the use of tags for ease of Aβ isolation, the formation of Aβ multimers within the time frame of extraction, or the need to reconstitute Aβ from a freeze–dried state. Here, we present a rapid protocol to produce highly pure and monomeric recombinant Aβ using a one-step ion exchange purification method and to label the peptide using a maleimide dye. The washing, solubilization, and purification steps take only 3 h. We also present a protocol for the isolation of Aβ-mCherry from mammalian cells.

α-Synuclein fibrillation products trigger the release of hexokinase I from mitochondria: Protection by curcumin, and possible role in pathogenesis of Parkinson's disease

Extensive research has shown that assembling of α-synuclein amyloid aggregates on mitochondria is an important mechanistic feature of Parkinson's disease (PD) and other Lewy body disorders. However, the molecular mechanism(s) of its neuronal toxicity remain unclear. Type 1 Hexokinase (HKI), a key enzyme in the control of brain glucose metabolism, plays an important role in protecting against mitochondrially-regulated apoptosis through reducing generation of reactive oxygen species (ROS). The release of mitochondrially-bound HKI causes a significant decrease in enzyme activity and triggers oxidative stress. Here, we have investigated the potency of amyloid fibrillation products arising from α-synuclein and hen egg white lysozyme (HEWL) for the release of HKI and ROS content enhancement in mitochondria isolated from rat brain. Results clearly indicate the capacity of the fibrillation products of α-synuclein, and not HEWL, to trigger release of HKI from the Type A binding site of mitochondria for the enzyme and to induce mitochondrial ROS enhancement in a dose-dependent manner. Moreover, we found that curcumin was very effective in preventing mitochondrial HKI release and ROS enhancement induced by α-synuclein fibrillation products. The pathophysiological significance of mitochondrial HKI activity and localization in pathogenesis of neurodegenerative disorders including PD are discussed. Taken together, these results may offer insight into a possible mechanism by which disease-related peptides and proteins may exert their neuronal toxicity.

Aggregation of disease-related peptides.

Protein misfolding and aggregation of amyloid proteins is the fundamental cause of more than 20 diseases. Molecular mechanisms of the self-assembly and the formation of the toxic aggregates are still elusive. Computer simulations have been intensively used to study the aggregation of amyloid peptides of various amino acid lengths related to neurodegenerative diseases. We review atomistic and coarse-grained simulations of short amyloid peptides aimed at determining their transient oligomeric structures and the early and late aggregation steps.

In situ AFM investigation of dual-mode self-assembling peptide

Nanostructures/patterns formed by biomolecules can produce different physicochemical properties in terms of hydrophobicity, zeta-potential, color, etc., which play paramount roles in life. Peptides, as the main bio-building blocks, can form nanostructures with different functions, either in solutions or on interfaces. Previously, we synthesized a short peptide with the inspiration of an Alzheimer’s disease-related peptide: amyloid β peptide (A-β), namely GAV-9, which can epitaxially self-assemble into regular nanofilaments on liquid–solid interfaces, and it was found that both the hydrophobicity and charge state of the interfaces can significantly influence its assembling behavior. It was also reported that another A-β-containing dipeptide, FF, can self-assemble into nanostructures in solutions. Owing to the close relationship between these two short peptides, it is interesting to conjugate them into a de novo peptide with two separated structural domains and study its self-assembling behavior. To this end, herein we have synthesized the GAV-FF peptide with a sequence of NH2-VGGAVVAGVFF-CONH2 and verified its self-assembling property using the in situ liquid-phase atomic force microscopy. The results show that the GAV-FF peptide can self-assemble into nanofilaments both in solutions and on aqueous–solid interfaces, but with different morphologies. The FF domain accelerates the template-assisted self-assembling (TASA) process of the GAV domain, which in return enhances the solubility of FF in aqueous solutions and further participates in the fibrillization of FF. The current results could help deepen the understanding of the aggregation mechanism of disease-related peptides and could also shed light on the strategies to create artificial bio-functional nanostructures/patterns, which hold a significant potential for biomedical applications.

Assembly of peptides in mica-graphene nanocapillaries controlled by confined water.

Water in nanoscale-confined geometries has unique physicochemical properties in contrast to bulk water, and is believed to play important roles in biological processes although there is less direct information available in the literature. Here, we report the self-assembly behaviors of a neurodegenerative disease related peptide termed GAV-9 encapsulated in mica-graphene nanocapillaries interacting with water nanofilms condensed under ambient conditions, based on atomic force microscopy (AFM) imaging and molecular dynamics (MD) simulations. The results revealed that, upon increase in the humidity, the GAV-9 peptide monomers adsorbed the confined water molecules and transitioned to unexpected hydrogel-like structures. Our MD simulations also suggested that in the confined mica-graphene nanocapillaries, the GAV-9 peptide monomers would indeed form water-rich hydrogel structures instead of highly ordered nanofilaments. The interfacial water confined in the mica-graphene nanocapillary is found to be crucial for such a transition. Moreover, the distribution of confined water layers largely depended on the locations of the preformed peptide nanofilaments, and the peptide nanofilaments further assembled into nanosheets with the water layer increasing, but depolymerized to amorphous peptide assemblies with the water layer decreasing. The polymerization and depolymerization of the peptide nanofilaments could be controlled in a reversible manner. Our results have supplied a simplified model system to uncover the effects of the confined interfacial water on the biological process at the molecular level.

Covalent Tethering and Residues with Bulky Hydrophobic Side Chains Enable Self-Assembly of Distinct Amyloid Structures.

Polymorphism is a common property of amyloid fibers that complicates their detailed structural and functional studies. Here we report experiments illustrating the chemical principles that enable the formation of amyloid polymorphs with distinct stoichiometric composition. Using appropriate covalent tethering we programmed self-assembly of a model peptide corresponding to the [20-41] fragment of human β2-microglobulin into fibers with either trimeric or dimeric amyloid cores. Using a set of biophysical and biochemical methods we demonstrated their distinct structural, morphological, and templating properties. Furthermore, we showed that supramolecular approaches in which the peptide is modified with bulky substituents can also be applied to modulate the formation of different fiber polymorphs. Such strategies, when applied to disease-related peptides and proteins, will greatly help in the evaluation of the biological properties of structurally distinct amyloids.

Opposite effect of Ca2+/Mg2+ ions on the aggregation of native and precursor-derived Aβ42

Work with the Alzheimer’s disease-related synthetic peptide beta-amyloid (Aβ) is a challenging task because of its disadvantageous dissolution properties and high propensity for aggregation. Recently, a new synthetic derivative, iso-Aβ42, has been introduced, which is a precursor of Aβ42, and it offers advantages as concerns its synthesis and use for sample preparation. These two Aβ forms showed high similarity in their biological effects, as well as in their main structural characteristics under well-chosen experimental circumstances. When we changed these conditions, considerable dissimilarities appeared in the aggregation properties of the two peptides. In the present study, the aggregation pathways of native and precursor-derived Aβ42 oligomers were compared in a physiological buffer with and without divalent metal ions (Ca2+/Mg2+). The presence of these ions influenced the Aβ conformations, the morphology as well as formation dynamics of aggregates in a different manner, as it was demonstrated by thioflavin-T-binding experiments, transmission electron microscopy and electronic circular dichroism measurements. Namely, the aggregation of native Aβ42 to fibrils was facilitated, while the aggregation of precursor-derived Aβ42 was hindered by these divalent metal ions. The observed differences in the aggregation had an impact also on the biological efficiency of native and precursor-derived Aβ42 as it was elucidated by viability assays with enhanced sensitivity on primary endothelial cell cultures. Using replica exchange molecular dynamics, we modeled the conformational ensembles of the two investigated Aβ variants evolving during preparation process. We found considerable differences in the probability distribution of the conformers that can explain the observed dissimilarities in their aggregation properties.

NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes

Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.

Large scale anomalous patterns of muscovite mica discovered by atomic force microscopy.

Muscovite mica is a widely used substrate because of its flatness. The large scale anomalous patterns of muscovite have been discovered by atomic force microscopy (AFM). These patterns distribute around the defects of the muscovite surface. By using different imaging modes and analyzing functions of AFM, these extraordinary patterns are thoroughly characterized, and it was revealed that some selected regularly aligned patterns mimic 2-D orthorhombic crystal systems surrounding the regular structure. However, such patterned nanostructures have no effects on the template-assisted self-assembly (or epitaxial growth) of a disease-related peptide GAV-9.

Alzheimer's disease-related peptide PS2V plays ancient, conserved roles in suppression of the unfolded protein response under hypoxia and stimulation of γ-secretase activity.

The PRESENILIN1 and PRESENILIN2 genes encode structurally related proteases essential for γ-secretase activity. Of nearly 200 PRESENILIN mutations causing early onset, familial Alzheimer's disease (FAD) only the K115Efx10 mutation of PSEN2 causes truncation of the open reading frame. If translated, the truncated product would resemble a naturally occurring isoform of PSEN2 named PS2V that is induced by hypoxia and found at elevated levels in late onset Alzheimer's disease (AD) brains. The function of PS2V is largely unexplored. We show that zebrafish possess a PS2V-like isoform, PS1IV, produced from the fish's PSEN1 rather than PSEN2 orthologous gene. The molecular mechanism controlling formation of PS2V/PS1IV was probably present in the ancient common ancestor of the PSEN1 and PSEN2 genes. Human PS2V and zebrafish PS1IV have highly divergent structures but conserved abilities to stimulate γ-secretase activity and to suppress the unfolded protein response (UPR) under hypoxia. The putative protein truncation caused by K115Efx10 resembles PS2V in its ability to increase γ-secretase activity and suppress the UPR. This supports increased Aβ levels as a common link between K115Efx10 early onset AD and sporadic, late onset AD. The ability of mutant variants of PS2V to stimulate γ-secretase activity partially correlates with their ability to suppress the UPR. The cytosolic, transmembrane and luminal domains of PS2V are all critical to its γ-secretase and UPR-suppression activities. Our data support a model in which chronic hypoxia in aged brains promotes excessive Notch signalling and accumulation of Aβ that contribute to AD pathogenesis.

Adsorption of β-amyloid oligomers on octadecanethiol monolayers

Hypothesisβ-Amyloid oligomers of different aggregation and physiological functions exhibit distinct adsorption behavior allowing them to be discriminated in preparations. ExperimentsTwo forms of amyloid oligomers, small 1–4nm and large 5–10nm were formulated using synthetic 42 amino acids β-amyloid peptide. Forms differ in their size and physiological function. A systematic study of adsorption of these amyloid species on self-assembled monolayers of octadecanethiol on gold was performed. Structural changes upon adsorption of oligomers were interrogated by the reflection absorption infrared spectroscopy. FindingsThe amount of adsorbed peptide material, as detected by surface plasmon resonance spectroscopy, is similar in case of both small and large oligomers. However, adsorption of small oligomers leads to a transformation from beta sheet rich to beta sheet depleted secondary structure. These changes were accompanied by the unique morphology patterns detectable by atomic force microscopy (AFM), while the quartz microbalance with dissipation indicated a formation of a compact adsorbate layer in case of small oligomers. These effects may be integrated and utilized in bioanalytical systems for sensing and detection of Alzheimer’s disease related peptide forms in artificial, and possibly, real preparations.

Roles of serum fibrinogen α chain‐derived peptides in Alzheimer's disease

To find a blood biomarker and disease-related peptides in Alzheimer's disease (AD), we comprehensively detected serum peptides. Ion intensity of serum peptides from 62 AD patients and 82 control subjects was measured by mass spectrometry. A total of 157 peptides were detected from 30 AD patients and 30 healthy control (HC) subjects. Sixty out of the 157 peptide profiles discriminated between the AD and HC groups. Sixteen out of the 60 peptides were identified, 10 out of which were fragments of a fibrinogen α chain (FIBA). Among the 10 peptides, four and six peptides were derived from fibrinopeptide A (FPA, Aα1-16) and the C-terminal region of the αC-domain (αCDC, Aα557-610), respectively. The profile of 10 FIBA-derived peptides combined with age discriminated between the two groups with an area under the receiver operating characteristic curve (AUROC) of 0.940. Validation of this model using a testing set of 32 AD patients and 19 HC subjects showed an AUROC of 0.717, sensitivity of 65.6%, and specificity of 73.7% by a cutoff value of 0.56420. Another value, 0.04029, showed sensitivity of 96.9%, suggesting that subjects with values less than 0.04029 rarely possess AD. FPA and αCDC showed increased ion intensity in the AD group compared with the HC group (p < 0.05). The profile of 10 FIBA-derived peptides combined with age would be a candidate biomarker for AD, which facilitates screening of the disease. The significant release of FPA and αCDC may be involved in the aberrant coagulation that leads to vascular damage in AD.

The Structure of Cross‐β Tapes and Tubes Formed by an Octapeptide, αSβ1

Elaborate morphology: The αSβ1 peptide, a fragment of α-synuclein, assembles into flat tapes consisting of a peptide bilayer, which can be modeled based on the cross-β structure found in amyloid proteins. The tapes are stabilized by hydrogen bonding, whilst the amphiphilic nature of the peptide results in the thin bilayer structure. To further stabilize the structure, these tapes may twist to form helical tapes, which subsequently close into nanotubes.