scholarly journals The Materials Science of Protein Aggregation

MRS Bulletin ◽  
2005 ◽  
Vol 30 (6) ◽  
pp. 452-457 ◽  
Author(s):  
D.L. Cox ◽  
H. Lashuel ◽  
K.Y.C. Lee ◽  
R.R.P. Singh
Keyword(s):  
Protein Aggregation ◽  
Conformational Change ◽  
Lipid Bilayers ◽  
Materials Science ◽  
Prion Diseases ◽  
Protein Structures ◽  
Biochemical Networks ◽  
Amyloid Formation ◽  
Biological Phenomena

AbstractNumerous human diseases are associated with conformational change and aggregation of proteins, including Alzheimer's, Parkinson's, prion diseases (such as mad cow disease), familial amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), Huntington's, and type II (mature onset) diabetes. In many cases, it has been demonstrated that conformational change and aggregation can occur outside living cells and complex biochemical networks. Hence, approaches from materials and physical science have enhanced our understanding of the role of protein aggregation in these diseases at the molecular and nanoscale levels. In this article, we will review what is known about these protein structures from the perspective of materials science, focusing on the details of emergent oligomeric and nanotube-like structures, their interactions with model lipid bilayers, how the structures relate to observed biological phenomena, and how protein aggregation and amyloid formation can be employed for the good in biology and materials science.

Prions: Protein Aggregation and Infectious Diseases

2009 ◽  
Vol 89 (4) ◽  
pp. 1105-1152 ◽  
Author(s):  
Adriano Aguzzi ◽  
Anna Maria Calella
Keyword(s):  
Protein Aggregation ◽  
Prion Diseases ◽  
Physiological Role ◽  
Infectious Agent ◽  
Normal Function ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Pathological Features ◽  
Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are inevitably lethal neurodegenerative diseases that affect humans and a large variety of animals. The infectious agent responsible for TSEs is the prion, an abnormally folded and aggregated protein that propagates itself by imposing its conformation onto the cellular prion protein (PrPC) of the host. PrPCis necessary for prion replication and for prion-induced neurodegeneration, yet the proximal causes of neuronal injury and death are still poorly understood. Prion toxicity may arise from the interference with the normal function of PrPC, and therefore, understanding the physiological role of PrPCmay help to clarify the mechanism underlying prion diseases. Here we discuss the evolution of the prion concept and how prion-like mechanisms may apply to other protein aggregation diseases. We describe the clinical and the pathological features of the prion diseases in human and animals, the events occurring during neuroinvasion, and the possible scenarios underlying brain damage. Finally, we discuss potential antiprion therapies and current developments in the realm of prion diagnostics.

scholarly journals Tuning microscale, retractable, membrane-breaking protein needles

2015 ◽  
Author(s):  
Jessica K Polka ◽  
Pamela A Silver
Keyword(s):  
Lipid Bilayers ◽  
Protein Structures ◽  
Open Reading Frames ◽  
Paramecium Tetraurelia ◽  
E Coli ◽  
Body State ◽  
High Throughput Assay ◽  
Reading Frames

The refractile (R) bodies found in Caedibacter taeniospiralis, a bacterial endosymbiont of Paramecium tetraurelia, are large, polymeric protein structures that can switch between two conformations. At cytoplasmic pH, they resemble coiled ribbons of protein 500nm in diameter. At low pH, they extend to form hollow needles up to 20 microns long. They can be expressed heterologously from an operon containing four short open reading frames and can function in vitro in diverse buffer conditions. In this study, R bodies purified from Escherichia coli were found to be capable of undergoing many consecutive extension-contraction cycles. Furthermore, the solubility of R bodies, which can easily be interpreted by eye, was found to correlate with their extension state. This macroscopic phenotype was used to develop a quantitative, high-throughput assay for R body state, enabling a visual screen of R body mutants defective in extension. The role of specific amino acids in extension was determined, and this information was used to construct rationally-designed mutants tailored to extend at higher pH. Furthermore, R bodies were able to rupture E. coli spheroplasts to release soluble proteins across lipid bilayers. Taken together, these results show that R bodies act as tunable, pH-actuated pistons suitable for a variety of membrane-breaking applications.

scholarly journals Effect of spin labelling on the aggregation kinetics of yeast prion protein Ure2

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Emilie N. Liu ◽  
Giovanna Park ◽  
Junsuke Nohara ◽  
Zhefeng Guo
Keyword(s):  
Protein Aggregation ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Aggregation Kinetics ◽  
Amyloid Formation ◽  
Yeast Prion ◽  
Aggregation Rate ◽  
Rate Limiting Step ◽  
Wide Range ◽  
Spin Labelling

Amyloid formation is involved in a wide range of neurodegenerative diseases including Alzheimer's and prion diseases. Structural understanding of the amyloid is critical to delineate the mechanism of aggregation and its pathological spreading. Site-directed spin labelling has emerged as a powerful structural tool in the studies of amyloid structures and provided structural evidence for the parallel in-register β-sheet structure for a wide range of amyloid proteins. It is generally accepted that spin labelling does not disrupt the structure of the amyloid fibrils, the end product of protein aggregation. The effect on the rate of protein aggregation, however, has not been well characterized. Here, we employed a scanning mutagenesis approach to study the effect of spin labelling on the aggregation rate of 79 spin-labelled variants of the Ure2 prion domain. The aggregation of Ure2 protein is the basis of yeast prion [URE3]. We found that all spin-labelled Ure2 mutants aggregated within the experimental timeframe of 15 to 40 h. Among the 79 spin-labelled positions, only five residue sites (N23, N27, S33, I35 and G42) showed a dramatic delay in the aggregation rate as a result of spin labelling. These positions may be important for fibril nucleation, a rate-limiting step in aggregation. Importantly, spin labelling at most of the sites had a muted effect on Ure2 aggregation kinetics, showing a general tolerance of spin labelling in protein aggregation studies.

scholarly journals Liquid condensates increase potency of amyloid fibril inhibitors

2020 ◽  
Author(s):  
Thomas C. T. Michaels ◽  
L. Mahadevan ◽  
Christoph A. Weber
Keyword(s):  
Phase Separation ◽  
Protein Aggregation ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Amyloid Formation ◽  
Physiological Processes ◽  
Parkinson’S Diseases ◽  
Spatio Temporal ◽  
Liquid Condensate

In living cells, liquid condensates form in the cytoplasm and nucleoplasm via phase separation and regulate physiological processes. They also regulate aberrant aggregation of amyloid fibrils, a process linked to Alzheimer’s and Parkinson’s diseases. In the absence of condensates it has been shown that amyloid aggregation can be inhibited by molecular chaperones and rationally designed drugs. However it remains unknown how this drug- or chaperone-mediated inhibition of amyloid fibril aggregation is affected by phase-separated condensates. Here we study the interplay between protein aggregation, its inhibition and liquid-liquid phase separation. Our key finding is that the potency of inhibitors of amyloid formation can be strongly enhanced. We show that the corresponding mechanism relies on the colocalization of inhibitors and aggregates inside the liquid condensate. We provide experimentally testable physicochemical conditions under which the increase of inhibitor potency is most pronounced. Our work highlights the role of spatio-temporal heterogeneity in curtailing aberrant protein aggregation and suggests design principles for amyloid inhibitors accounting for partitioning of drugs into liquid condensates.

Epigenetic Regulator Signatures in Regenerative Capacity

2019 ◽  
Vol 14 (7) ◽  
pp. 598-606
Author(s):  
Sarah Albogami
Keyword(s):  
Epigenetic Regulation ◽  
Animal Species ◽  
Current Knowledge ◽  
Regeneration Process ◽  
Body Parts ◽  
Lysine Methylation ◽  
Regenerative Capacity ◽  
Biological Phenomena ◽  
Epigenetic Regulator

Background:: Regeneration is the process by which body parts lost as a result of injury are replaced, as observed in certain animal species. The root of regenerative differences between organisms is still not very well understood; if regeneration merely recycles developmental pathways in the adult form, why can some animals regrow organs whereas others cannot? In the regulation of the regeneration process as well as other biological phenomena, epigenetics plays an essential role. Objective:: This review aims to demonstrate the role of epigenetic regulators in determining regenerative capacity. Results:: In this review, we discuss the basis of regenerative differences between organisms. In addition, we present the current knowledge on the role of epigenetic regulation in regeneration, including DNA methylation, histone modification, lysine methylation, lysine methyltransferases, and the SET1 family. Conclusion:: An improved understanding of the regeneration process and the epigenetic regulation thereof through the study of regeneration in highly regenerative species will help in the field of regenerative medicine in future.

scholarly journals The search for new materials and the role of novel processing routes

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Peter J. Wellmann
Keyword(s):  
Materials Science ◽  
Research Society ◽  
Subsequent Treatment ◽  
European Council ◽  
Trial And Error ◽  
Human History ◽  
New Materials ◽  
Materials Research ◽  
Novel Processing

AbstractThroughout human history, most further developments or new achievements were accompanied by new materials or new processes that enabled the technologic progress. With concrete devices and applications in mind, synthesis and subsequent treatment of materials naturally went along with the progress. The aim of the underlying article is to spot the role of optimization, of discovery, of trial-and-error approaches, of fundamentals and curiosity driven design and development. In a consecutive examination, five missions addressing the challenges facing our world (identified by the European Council) will be cross linked with seven topical areas from materials science defined by the European Materials Research Society. The scope of this examination is to identify approaches and methods to further develop and innovate materials which form the basis of the anticipated solutions.

scholarly journals Neuroimmune Response Mediated by Cytokines in Natural Scrapie after Chronic Dexamethasone Treatment

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 204
Author(s):  
Isabel M. Guijarro ◽  
Moisés Garcés ◽  
Pol Andrés-Benito ◽  
Belén Marín ◽  
Alicia Otero ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Global Approach ◽  
Profile Data ◽  
Dexamethasone Treatment ◽  
New Approach ◽  
Complex Interactions ◽  
Natural Scrapie ◽  
Anti Inflammatory

The actual role of prion protein-induced glial activation and subsequent cytokine secretion during prion diseases is still incompletely understood. The overall aim of this study is to assess the effect of an anti-inflammatory treatment with dexamethasone on different cytokines released by neuroglial cells that are potentially related to neuroinflammation in natural scrapie. This study emphasizes the complex interactions existent among several pleiotropic neuromodulator peptides and provides a global approach to clarify neuroinflammatory processes in prion diseases. Additionally, an impairment of communication between microglial and astroglial populations mediated by cytokines, mainly IL-1, is suggested. The main novelty of this study is that it is the first one assessing in situ neuroinflammatory activity in relation to chronic anti-inflammatory therapy, gaining relevance because it is based on a natural model. The cytokine profile data would suggest the activation of some neurotoxicity-associated route. Consequently, targeting such a pathway might be a new approach to modify the damaging effects of neuroinflammation.

scholarly journals Lipid Transporters Beam Signals from Cell Membranes

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 562
Author(s):  
Miliça Ristovski ◽  
Danny Farhat ◽  
Shelly Ellaine M. Bancud ◽  
Jyh-Yeuan Lee
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Lipid Composition ◽  
Structural Integrity ◽  
Current Knowledge ◽  
Integral Membrane Proteins ◽  
Cellular Membranes ◽  
Cytoplasmic Proteins ◽  
Lipid Transporters

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.

scholarly journals Valorization of Apple Peels through the Study of the Effects on the Amyloid Aggregation Process of κ-Casein

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2371
Author(s):  
Valeria Guarrasi ◽  
Giacoma Cinzia Rappa ◽  
Maria Assunta Costa ◽  
Fabio Librizzi ◽  
Marco Raimondo ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Environmental Sustainability ◽  
Bovine Milk ◽  
Amyloid Formation ◽  
Aggregation Process ◽  
Amyloid Aggregation ◽  
Social Challenges ◽  
Force Microscopy ◽  
Atomic Force ◽  
Apple Peels

Waste valorization represents one of the main social challenges when promoting a circular economy and environmental sustainability. Here, we evaluated the effect of the polyphenols extracted from apple peels, normally disposed of as waste, on the amyloid aggregation process of κ-casein from bovine milk, a well-used amyloidogenic model system. The effect of the apple peel extract on protein aggregation was examined using a thioflavin T fluorescence assay, Congo red binding assay, circular dichroism, light scattering, and atomic force microscopy. We found that the phenolic extract from the peel of apples of the cultivar “Fuji”, cultivated in Sicily (Caltavuturo, Italy), inhibited κ-casein fibril formation in a dose-dependent way. In particular, we found that the extract significantly reduced the protein aggregation rate and inhibited the secondary structure reorganization that accompanies κ-casein amyloid formation. Protein-aggregated species resulting from the incubation of κ-casein in the presence of polyphenols under amyloid aggregation conditions were reduced in number and different in morphology.

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