5,393 results match your criteria form fibrils


Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.

J Phys Chem B 2021 Jun 15. Epub 2021 Jun 15.

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611, United States.

Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications. Read More

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A fluorescent molecular imaging probe with selectivity for soluble tau aggregated protein.

Chem Sci 2020 Apr 21;11(18):4773-4778. Epub 2020 Apr 21.

Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge Cambridge UK

Soluble forms of aggregated tau misfolded protein, generally termed oligomers, are considered to be the most toxic species of the different assembly states that are the pathological components of neurodegenerative disorders. Therefore, a critical biomedical need exists for imaging probes that can identify and quantify them. We have designed and synthesized a novel fluorescent probe, for which binding and selectivity profiles towards aggregated tau and Aβ proteins were assessed. Read More

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Small molecule-mediated co-assembly of amyloid-β oligomers reduces neurotoxicity through promoting non-fibrillar aggregation.

Chem Sci 2020 Jun 22;11(27):7158-7169. Epub 2020 Jun 22.

State Key Laboratory of Coordination Chemistry, Nanjing University Nanjing 210093 P. R. China

Amyloid-β (Aβ) oligomers, particularly low molecular weight (LMW) oligomers, rather than fibrils, contribute very significantly to the onset and progression of Alzheimer's Disease (AD). However, due to the inherent heterogeneity and metastability of oligomers, most of the conventional anti-oligomer therapies have indirectly modulated oligomers' toxicity through manipulating Aβ self-assembly to reduce oligomer levels, which are prone to suffering from the risk of regenerating toxic oligomers from the products of modulation. To circumvent this disadvantage, we demonstrate, for the first time, rational design of rigid pincer-like scaffold-based small molecules with blood-brain barrier permeability that specifically co-assemble with LMW Aβ oligomers through directly binding to the exposed hydrophobic regions of oligomers to form non-fibrillar, degradable, non-toxic co-aggregates. Read More

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From Kuru to Alzheimer: a personal outlook.

Authors:
Maurizio Brunori

Protein Sci 2021 Jun 12. Epub 2021 Jun 12.

Accademia Nazionale dei Lincei and Dipartimento di Scienze Biochimiche "A. Rossi Fanelli," Sapienza Università di Roma, Rome, Italy.

Seventy years ago we learned from Chris Anfinsen that the stereochemical code necessary to fold a protein is embedded into its amino acid sequence. In water, protein morphogenesis is a spontaneous reversible process leading from an ensemble of disordered structures to the ordered functionally competent protein; conforming to Aristotle's definition of substance, the synolon of matter and form. The overall process of folding is generally consistent with a two state transition between the native and the denatured protein: not only the denatured state is an ensemble of several structures, but also the native protein populates distinct functionally relevant conformational (sub)states. Read More

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Machine learning analyses of antibody somatic mutations predict immunoglobulin light chain toxicity.

Nat Commun 2021 06 10;12(1):3532. Epub 2021 Jun 10.

Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.

In systemic light chain amyloidosis (AL), pathogenic monoclonal immunoglobulin light chains (LC) form toxic aggregates and amyloid fibrils in target organs. Prompt diagnosis is crucial to avoid permanent organ damage, but delayed diagnosis is common because symptoms usually appear only after strong organ involvement. Here we present LICTOR, a machine learning approach predicting LC toxicity in AL, based on the distribution of somatic mutations acquired during clonal selection. Read More

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Amyloidosis with Cardiac Involvement: Identification, Characterization, and Management.

Curr Hematol Malig Rep 2021 Jun 9. Epub 2021 Jun 9.

Department of Hematology, City of Hope, 1500 E Duarte Rd. Duarte, CA, Duarte, CA, 91010, USA.

Purpose Of Review: Amyloidosis is a protein deposition disease whereby a variety of precursor proteins form insoluble fibrils that deposit in tissues, causing organ dysfunction and, many times, death. Accurate characterization of the disease based on the nature of the precursor protein, organ involvement, and extent of disease is paramount to guide management. Cardiac amyloidosis is critical to understand because of its impact on prognosis and new treatment options available. Read More

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COVID-19 AND CHILDREN: COMPLICATIONS AND LATE OUTCOMES.

Georgian Med News 2021 Apr(313):124-127

Tbilisi State Medical University, G. Zhvania Pediatric Academic Clinic, Georgia.

Since December 2019, Covid-19 has become a challenge for doctors around the world, including pediatricians. In most infected children, the disease manifests itself in a mild or is char- acterized by a subclinical course. At the same time, in some cases, a severe clinical picture of the so-called late Covid disease may develop, in the form of a multisystem syndrome and other complications. Read More

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Lewy body-associated proteins: victims, instigators, or innocent bystanders? The case of AIMP2 and alpha-synuclein.

Neurobiol Dis 2021 Jun 6;156:105417. Epub 2021 Jun 6.

Laboratory of Molecular and Chemical Biology of Neurodegeneration, School of Life Sciences, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Lewy bodies (LBs), one of the neuropathological defining hallmarks of Parkinson's disease (PD), are composed of a complex mixture of alpha-synuclein (aSyn) filaments and hundreds of proteins, lipids, and membranous organelles. However, these proteins' role in aSyn aggregation and the biogenesis of LBs remains poorly understood. Previous studies have focused on investigating the role of these proteins as modifiers of aSyn aggregation, inclusion formation, and toxicity; very often, one protein at a time. Read More

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Mechanism of collagen folding propagation studied by Molecular Dynamics simulations.

PLoS Comput Biol 2021 Jun 8;17(6):e1009079. Epub 2021 Jun 8.

Center for Functional Protein Assemblies, Technische Universität München, Garching, Germany.

Collagen forms a characteristic triple helical structure and plays a central role for stabilizing the extra-cellular matrix. After a C-terminal nucleus formation folding proceeds to form long triple-helical fibers. The molecular details of triple helix folding process is of central importance for an understanding of several human diseases associated with misfolded or unstable collagen fibrils. Read More

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Effects of sedimentation, microgravity, hydrodynamic mixing and air-water interface on α-synuclein amyloid formation.

Chem Sci 2020 Mar 10;11(14):3687-3693. Epub 2020 Mar 10.

Laboratory of Physics of Living Matter, École Polytechnique Fédérale de Lausanne (EPFL) CH-1015 Lausanne Switzerland

The formation of amyloid fibrils is a characterizing feature of a range of protein misfolding diseases, including Parkinson's disease. The propensity of native proteins to form such amyloid fibril, both and , is highly sensitive to the surrounding environment, which can alter the aggregation kinetics and fibrillization mechanisms. Here, we investigate systematically the influence of several representative environmental stimuli on α-synuclein aggregation, including hydrodynamic mixing, the presence of an air-water interface and sedimentation. Read More

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Exosomal and vesicle-free tau seeds-propagation and convergence in endolysosomal permeabilization.

FEBS J 2021 Jun 6. Epub 2021 Jun 6.

Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland, Brisbane, QLD, Australia.

In Alzheimer's disease (AD), β-amyloid peptides aggregate to form amyloid plaques, and the microtubule-associated protein tau forms neurofibrillary tangles. However, severity and duration of AD correlate with the stereotypical emergence of tau tangles throughout the brain, suggestive of a gradual region-to-region spreading of pathological tau. The current notion in the field is that misfolded tau seeds propagate transsynaptically and corrupt the proper folding of soluble tau in recipient neurons. Read More

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Mapping the fibril core of the prion subdomain of the mammalian CPEB3 that is involved in long term memory retention.

J Mol Biol 2021 May 31:167084. Epub 2021 May 31.

School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram, Trivandrum-695551 (India). Electronic address:

Long-term memory storage is modulated by the prion nature of CPEB3 forming the molecular basis for the maintenance of synaptic facilitation. Here we report that the first prion sub-domain PRD1 of mouse CPEB3 can autonomously form amyloid fibrils in vitro and punctate-like structures in vivo. A ninety-four amino acid sequence within the PRD1 domain, PRD1-core, displays high propensity towards aggregation and associated amyloid characteristics. Read More

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(-)-Oleocanthal Nutraceuticals for Alzheimer's Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model.

Nutrients 2021 May 18;13(5). Epub 2021 May 18.

School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA.

Alzheimer's disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aβ-amyloid (Aβ) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid -(-)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. Read More

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Effects of Alpha-Synuclein Targeted Antisense Oligonucleotides on Lewy Body-Like Pathology and Behavioral Disturbances Induced by Injections of Pre-Formed Fibrils in the Mouse Motor Cortex.

J Parkinsons Dis 2021 May 26. Epub 2021 May 26.

Department of Neurology, Oregon Health & Science University, Portland, OR, USA.

Background: Alpha-synuclein (αsyn) characterizes neurodegenerative diseases known as synucleinopathies. The phosphorylated form (psyn) is the primary component of protein aggregates known as Lewy bodies (LBs), which are the hallmark of diseases such as Parkinson's disease (PD). Synucleinopathies might spread in a prion-like fashion, leading to a progressive emergence of symptoms over time. Read More

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Modeling of bending and torsional stiffnesses of bone at sub-microscale: Effect of curved mineral lamellae.

J Biomech 2021 Jun 15;123:110531. Epub 2021 May 15.

Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 West Green Street, Urbana, IL 61801, USA. Electronic address:

Recent transmission electron microscopy images of transverse sections of human cortical bone showed that mineral lamellae (polycrystalline sheets of apatite crystals) form arcuate multi-radius patterns around collagen fibrils. The 3-6 nm thick mineral lamellae are arranged in stacks of 3-20 layers and curve around individual fibrils, few fibrils, and higher numbers of collagen fibrils. We evaluate the effect of these stacked mineral lamellae with various radius of curvature patterns on the elastic bending and torsional responses of bone at the sub-microscale using a finite element method. Read More

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Polyphenol-solubility alters amyloid fibril formation of α-synuclein.

Protein Sci 2021 May 27. Epub 2021 May 27.

Institute for Protein Research, Osaka University, Osaka, Japan.

Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Amyloid fibrils form above the solubility of amyloidogenic proteins or peptides upon breaking supersaturation, followed by a nucleation and elongation mechanism, which is similar to the crystallization of solutes. Many additives, including salts, detergents, and natural compounds, promote or inhibit amyloid formation. Read More

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Droplet and fibril formation of the functional amyloid Orb2.

J Biol Chem 2021 May 24:100804. Epub 2021 May 24.

Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, CA 90033, Los Angeles, USA. Electronic address:

The functional amyloid Orb2 belongs to the cytoplasmic polyadenylation element binding (CPEB) protein family and plays an important role in long-term memory formation in Drosophila. The Orb2 domain structure combines RNA recognition motifs with low complexity sequences similar to many RNA binding proteins shown to form protein droplets via liquid-liquid phase separation (LLPS) in vivo and in vitro. This similarity suggests that Orb2 might also undergo LLPS. Read More

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Staphylococcus aureus N-terminus formylated δ-toxin tends to form amyloid fibrils, while the deformylated δ-toxin tends to form functional oligomer complexes.

Virulence 2021 Dec;12(1):1418-1437

State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Beijing, China.

The community-associated Methicillin-resistant strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many strains. Read More

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December 2021

Polymerization of misfolded Z alpha-1 antitrypsin protein lowers CX3CR1 expression in human PBMCs.

Elife 2021 May 18;10. Epub 2021 May 18.

Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.

Expression levels of CX3CR1 (C-X3-C motif chemokine receptor 1) on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host's misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Read More

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Insights into the molecular mechanism of amyloid filament formation: Segmental folding of α-synuclein on lipid membranes.

Sci Adv 2021 May 14;7(20). Epub 2021 May 14.

Department of NMR-Based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.

Recent advances in the structural biology of disease-relevant α-synuclein fibrils have revealed a variety of structures, yet little is known about the process of fibril aggregate formation. Characterization of intermediate species that form during aggregation is crucial; however, this has proven very challenging because of their transient nature, heterogeneity, and low population. Here, we investigate the aggregation of α-synuclein bound to negatively charged phospholipid small unilamellar vesicles. Read More

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Inclusion of the C-Terminal Domain in the β-Sheet Core of Heparin-Fibrillized Three-Repeat Tau Protein Revealed by Solid-State Nuclear Magnetic Resonance Spectroscopy.

J Am Chem Soc 2021 May 13;143(20):7839-7851. Epub 2021 May 13.

Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.

Many neurodegenerative diseases such as Alzheimer's disease are characterized by pathological β-sheet filaments of the tau protein, which spread in a prion-like manner in patient brains. To date, high-resolution structures of tau filaments obtained from patient brains show that the β-sheet core only includes portions of the microtubule-binding repeat domains and excludes the C-terminal residues, indicating that the C-terminus is dynamically disordered. Here, we use solid-state NMR spectroscopy to identify the β-sheet core of full-length 0N3R tau fibrillized using heparin. Read More

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EGFR Aggregation in the Brain.

ACS Chem Neurosci 2021 06 12;12(11):1833-1834. Epub 2021 May 12.

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.

Recent findings showed that preformed fibrils (PFFs) of misfolded proteins, including α-synuclein (α-syn) and amyloid-β (Aβ), activate EGFR in cell cultures and animal models of amyloid propagation. Comparing these supramolecular structures to normal EGFR ligands such as EGF and HB-EGF suggests that these PFFs might trigger the formation of high order clustering of EGFR that stimulates the aggregation of EGFR tyrosine kinase domain (EGFR-TKD) which is known to form fibrils. Subsequently, self-assembled fibril of EGFR-TKDs itself can serve as a seed to induce aggregation of monomeric forms of misfolded proteins in cytoplasm or endosomes. Read More

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L-Dopa in small peptides: an amazing functionality to form supramolecular materials.

Org Biomol Chem 2021 Jun;19(21):4622-4636

Dipartimento di Chimica Giacomo Ciamician - Università di Bologna - Via Selmi, 2-40126 Bologna, Italy.

l-Dopa (3,4-dihydroxyphenylalanine) is a chiral amino acid generated via biosynthesis from l-tyrosine in plants and some animals. The presence of multiple interacting sites makes l-Dopa a multifunctional building block for the preparation of supramolecular materials. The possibility to form hydrogen bonds and the presence of the aromatic ring allow l-Dopa molecules to interact through a series of non-covalent interactions. Read More

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Distinctive roles of fibrillar collagen I and collagen III in mediating fibroblast-matrix interaction: A nanoscopic study.

Biochem Biophys Res Commun 2021 Jun 8;560:66-71. Epub 2021 May 8.

Department of Chemistry, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, IL, 60616, USA. Electronic address:

One major goal in tissue engineering is to create functional materials, mimicking scaffolds in native tissues, to modulate cell function for tissue repair. Collagen is the most abundant structural protein in human body. Though collagen I (COLI) and collagen III (COLIII) are the predominant collagen types in connective tissues and they form stable hybrid fibrils at varied ratios, cell responses to the hybrid matrices are underinvestigated. Read More

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Revisiting the classification of squamate adhesive setae: historical, morphological and functional perspectives.

R Soc Open Sci 2021 Feb 17;8(2):202039. Epub 2021 Feb 17.

Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4.

Research on gecko-based adhesion has become a truly interdisciplinary endeavour, encompassing many disciplines within the natural and physical sciences. Gecko adhesion occurs by the induction of van der Waals intermolecular (and possibly other) forces between substrata and integumentary filaments (setae) terminating in at least one spatulate tip. Gecko setae have increasingly been idealized as structures with uniform dimensions and a particular branching pattern. Read More

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February 2021

Carbon Quantum Dots for Treatment of Amyloid Disorders.

ACS Appl Nano Mater 2021 Mar 4;4(3):2423-2433. Epub 2021 Mar 4.

Department of Chemistry and Biochemistry, The University of Texas at El Paso (UTEP), El Paso, Texas 79968, United States.

Prion-like amyloids self-template and form toxic oligomers, protofibrils, and fibrils from their soluble monomers; a phenomenon that has been implicated in the onset and progress of neurodegenerative disorders such as Alzheimer's (AD), Parkinson's (PD), Huntington's, and systemic lysozyme amyloidosis. Carbon quantum dots (CQDs), sourced from Na-citrate as a carbon precursor were synthesized and characterized before being tested for their ability to intervene in amyloidogenic (fibril-forming) trajectories. Hen-egg white lysozyme (HEWL) served as a model amyloidogenic protein. Read More

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Exploring the inhibitory effects of liquiritigenin against tau fibrillation and related neurotoxicity as a model of preventive care in Alzheimer's disease.

Int J Biol Macromol 2021 May 6;183:1184-1190. Epub 2021 May 6.

Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address:

Aggregation of tau protein into the form of insoluble amyloid fibrils is linked with Alzheimer's disease. The identification of potential small molecules that can inhibit tau protein from undergoing aggregation has received a great deal of interest, recently. In the present study, the possible inhibitory effects of liquiritigenin as a member of chiral flavanone family on tau amyloid fibrils formation and their resulting neurotoxicity were assessed by different biophysical and cellular assays. Read More

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Role of Water Molecules and Helix Structure Stabilization in the Laser-Induced Disruption of Amyloid Fibrils Observed by Nonequilibrium Molecular Dynamics Simulations.

J Phys Chem B 2021 05 7;125(19):4964-4976. Epub 2021 May 7.

IR Free Electron Laser Research Center, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Noda, Chiba 278-8510, Japan.

Water plays a crucial role in the formation and destruction of biomolecular structures. The mechanism for destroying biomolecular structures was thought to be an active breaking of hydrogen bonds by water molecules. However, using nonequilibrium molecular dynamics simulations, in which an amyloid-β amyloid fibril was destroyed via infrared free-electron laser (IR-FEL) irradiation, we discovered a new mechanism, in which water molecules disrupt protein aggregates. Read More

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Promoted Aggregation of Aβ on Lipid Bilayers in an Open Flowing System.

J Phys Chem Lett 2021 May 6;12(18):4453-4460. Epub 2021 May 6.

Faculty of Science, Yamagata University, 1-4-12 Kojirakawa, Yamagata 990-8560, Japan.

Self-assembly of amyloid-β (Aβ) peptides in nonequilibrium, flowing conditions is associated with pathogenesis of Alzheimer's disease. We examined the role of biologically relevant, nonequilibrium, flowing conditions in the desorption, diffusion, and integration of Aβ-lipid assemblies at the membrane surface using a microchannel connected with microsyringes. A 1,2-dimyristoyl--glycero-3-phosphocholine (DMPC) bilayer was formed on a glass substrate and incubated in Aβ solution under either a quiescent condition (no flow) or flowing condition for 24 h. Read More

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α-synuclein aggregates induce c-Abl activation and dopaminergic neuronal loss by a feed-forward redox stress mechanism.

Prog Neurobiol 2021 Jul 2;202:102070. Epub 2021 May 2.

Department of Neurology, University of California San Francisco, United States; Neurology Service, San Francisco Veterans Affairs Health Care System, United States. Electronic address:

Oxidative stress and α-synuclein aggregation both drive neurodegeneration in Parkinson's disease, and the protein kinase c-Abl provides a potential amplifying link between these pathogenic factors. Suppressing interactions between these factors may thus be a viable therapeutic approach for this disorder. To evaluate this possibility, pre-formed α-synuclein fibrils (PFFs) were used to induce α-synuclein aggregation in neuronal cultures. Read More

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