scholarly journals Amyloidogenic Peptides in Human Neuro-Degenerative Diseases and in Microorganisms: A Sorrow Shared Is a Sorrow Halved?

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 925 ◽  
Author(s):  
Kristina Endres
Keyword(s):  
Neurodegenerative Diseases ◽  
Self Assembly ◽  
Amyloid Β ◽  
Degenerative Diseases ◽  
Human Beings ◽  
Precursor Proteins ◽  
Long Time ◽  
Health And Disease ◽  
Amyloidogenic Peptides ◽  
Toxic Peptides

The term “amyloid” refers to proteinaceous deposits of peptides that might be generated from larger precursor proteins e.g., by proteolysis. Common to these peptides is a stable cross-β dominated secondary structure which allows self-assembly, leading to insoluble oligomers and lastly to fibrils. These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer’s disease (Amyloid-β peptides). However, they also exert physiological functions such as in release of deposited hormones in human beings. In the light of the rediscovery of our microbial commensals as important companions in health and disease, the fact that microbes also possess amyloidogenic peptides is intriguing. Transmission of amyloids by iatrogenic means or by consumption of contaminated meat from diseased animals is a well-known fact. What if also our microbial commensals might drive human amyloidosis or suffer from our aggregated amyloids? Moreover, as the microbial amyloids are evolutionarily older, we might learn from these organisms how to cope with the sword of Damocles forged of endogenous, potentially toxic peptides. This review summarizes knowledge about the interplay between human amyloids involved in neurodegenerative diseases and microbial amyloids.

scholarly journals Mechanism of Amyloid Gel Formation by Several Short Amyloidogenic Peptides

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3129
Author(s):  
Oxana V. Galzitskaya ◽  
Olga M. Selivanova ◽  
Elena Y. Gorbunova ◽  
Leila G. Mustaeva ◽  
Viacheslav N. Azev ◽  
...  
Keyword(s):  
Cell Wall ◽  
Neurodegenerative Diseases ◽  
Yeast Cell ◽  
Structure Formation ◽  
Self Assembly ◽  
The Body ◽  
Gel Formation ◽  
Domains Of Life ◽  
Amyloidogenic Peptides ◽  
Quaternary Structures

Under certain conditions, many proteins/peptides are capable of self-assembly into various supramolecular formations: fibrils, films, amyloid gels. Such formations can be associated with pathological phenomena, for example, with various neurodegenerative diseases in humans (Alzheimer’s, Parkinson’s and others), or perform various functions in the body, both in humans and in representatives of other domains of life. Recently, more and more data have appeared confirming the ability of many known and, probably, not yet studied proteins/peptides, to self-assemble into quaternary structures. Fibrils, biofilms and amyloid gels are promising objects for the developing field of research of nanobiotechnology. To develop methods for obtaining nanobiomaterials with desired properties, it is necessary to study the mechanism of such structure formation, as well as the influence of various factors on this process. In this work, we present the results of a study of the structure of biogels formed by four 10-membered amyloidogenic peptides: the VDSWNVLVAG peptide (AspNB) and its analogue VESWNVLVAG (GluNB), which are amyloidogenic fragments of the glucantransferase Bgl2p protein from a yeast cell wall, and amyloidogenic peptides Aβ(31–40), Aβ(33–42) from the Aβ(1–42) peptide. Based on the analysis of the data, we propose a possible mechanism for the formation of amyloid gels with these peptides.

scholarly journals Spontaneous Self-assembly of Amyloid β (1-40) into Dimers

2019 ◽  
Author(s):  
Mohtadin Hashemi ◽  
Yuliang Zhang ◽  
Zhengjian Lv ◽  
Yuri L. Lyubchenko
Keyword(s):  
Molecular Dynamics ◽  
Self Assembly ◽  
Amyloid Β ◽  
Conformational Transitions ◽  
Terminal Region ◽  
The Self ◽  
Hydrophobic Region ◽  
Peptide Interactions ◽  
Long Time ◽  
Dynamics Simulations

AbstractThe self-assembly and fibrillation of amyloid β (Aβ) proteins is the neuropathological hallmark of Alzheimer’s disease. However, the molecular mechanism of how disordered monomers assemble into aggregates remains largely unknown. In this work, we characterize the assembly of Aβ (1-40) monomers into dimers using long-time molecular dynamics simulations. Upon interaction, the monomers undergo conformational transitions, accompanied by change of the structure, leading to the formation of a stable dimer. The dimers are primarily stabilized by interactions in the N-terminal region (residues 5-12), in the central hydrophobic region (residues 16-23), and in the C-terminal region (residues 30-40); with inter-peptide interactions focused around the N- and C- termini. The dimers do not contain long β-strands that are usually found in fibrils.

scholarly journals An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Devkee M. Vadukul ◽  
Céline Vrancx ◽  
Pierre Burguet ◽  
Sabrina Contino ◽  
Nuria Suelves ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Self Assembly ◽  
Critical Nucleus ◽  
Amyloid Fibril ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
The Self ◽  
Aβ Peptide ◽  
Amyloid Fibril Formation ◽  
Secretase Activity

AbstractA key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers.

scholarly journals Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer’s disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Smita Eknath Desale ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Amyloid Β ◽  
Dietary Fatty Acids ◽  
Receptor Expression ◽  
Actin Binding ◽  
Actin Remodeling ◽  
Protein Deposits

AbstractAlzheimer’s disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupts signal transduction in neurons and other glia cells. The pathological protein in neurodegenerative diseases, Tau and amyloid-β contribute to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-β in Alzheimer’s disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. Phosphatidylinositol 3,4,5-triphosphate (PI 3, 4, 5-P3) involves in phagocytic cup formation, cell polarization, whereas Phosphatidylinositol 4,5-bisphosphate (PI 4, 5-P2)-mediates the process of phagosomes formation and further its fusion with early endosome.. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. The ratio and types of fatty acid intake can influence the intracellular secondary lipid messengers along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The Amyloid-β deposits and extracellular Tau seeds disrupt phosphatidylinositides level and actin cytoskeletal network that hamper microglial-signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. Further we are interested to understand phosphoinositide-based signaling cascades in phagocytosis and actin remodeling.

Hydrophobicity and Conformational Change as Mechanistic Determinants for Nonspecific Modulators of Amyloid β Self-Assembly

Biochemistry ◽  
2011 ◽  
Vol 51 (1) ◽  
pp. 126-137 ◽  
Author(s):  
Axel Abelein ◽  
Benedetta Bolognesi ◽  
Christopher M. Dobson ◽  
Astrid Gräslund ◽  
Christofer Lendel
Keyword(s):  
Conformational Change ◽  
Self Assembly ◽  
Amyloid Β

scholarly journals DNAJB6b is Downregulated in Synucleinopathies

2021 ◽  
pp. 1-13
Author(s):  
Jonas Folke ◽  
Sertan Arkan ◽  
Isak Martinsson ◽  
Susana Aznar ◽  
Gunnar Gouras ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Substantia Nigra Pars Compacta ◽  
Endogenous Protein ◽  
Highly Sensitive ◽  
Brain Material ◽  
Health And Disease ◽  
Isoform B

Background: α-synuclein (α-syn) aggregation contributes to the progression of multiple neurodegenerative diseases. We recently found that the isoform b of the co-chaperone DNAJB6 is a strong suppressor of a-syn aggregation in vivo and in vitro. However, nothing is known about the role of the endogenous isoform b of DNAJB6 (DNAJB6b) in health and disease, due to lack of specific antibodies. Objective: Here we generated a novel anti-DNAJB6b antibody to analyze the localization and expression this isoform in cells, in tissue and in clinical material. Methods: To address this we used immunocytochemistry, immunohistochemistry, as well as a novel quantitative DNAJB6 specific ELISA method. Results: The endogenous protein is mainly expressed in the cytoplasm and in neurites in vitro, where it is found more in dendrites than in axons. We further verified in vivo that DNAJB6b is expressed in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), which is a neuronal subpopulation highly sensitive to α-syn aggregation, that degenerate to a large extend in patients with Parkinson’s disease (PD) and multiple system atrophy (MSA). When we analyzed the expression levels of DNAJB6b in brain material from PD and MSA patients, we found a downregulation of DNAJB6b by use of ELISA based quantification. Interestingly, this was also true when analyzing tissue from patients with progressive supranuclear palsy, a taupathic atypical parkinsonian disorder. However, the total level of DNAJB6 was upregulated in these three diseases, which may indicate an upregulation of the other major isoform of DNAJB6, DNAJB6a. Conclusion: This study shows that DNAJB6b is downregulated in several different neurodegenerative diseases, which makes it an interesting target to further investigate in relation to amyloid protein aggregation and disease progression.

Adolescência, mídia e drogas: O condicionamento do humano através de mecanismos midiáticos

2021 ◽  
Author(s):  
Marciano Tribess
Keyword(s):  
Children And Adolescents ◽  
Mass Culture ◽  
Preventive Strategy ◽  
Human Being ◽  
Aldous Huxley ◽  
Human Beings ◽  
Society Of The Spectacle ◽  
Long Time ◽  
Michel Henry ◽  
The Media

This book presents the influence exerted by the media on children and adolescents in relation to the early experimentation with psychoactive substances. And the pedagogical-theological intervention as a preventive strategy. The influence on the human being through media mechanisms that condition him to the action expected by the conditioning, has been studied for a long time, by several authors such as Aldous Huxley with his book "Admirável Mundo Novo" that already addressed the conditionality of the human since the decade of 30. In the following decades, other theorists such as Edgar Morin and Guy Debord, analyzed how the human being is conditioned through mass culture and the society of the spectacle. The reality presented in relation to the conditioning of children and adolescents through the media has propelled the author, to seek preventive ways regarding the conditionality of human beings through the media. For that, it analyzed theorists like Paulo Freire and Michel Henry and their discoveries about the mediation of knowledge and the analysis of the Words of Christ and how they can contribute in the elaboration of pedagogical-theological interventions.

Comparativa de modelos multivariados basados en aprendizaje automático para la predicción del riesgo de diabetes en etapas tempranas

2021 ◽  
Author(s):  
◽  
Zayra Ramírez Gaytán
Keyword(s):  
World Health ◽  
Degenerative Diseases ◽  
Decision Tree Algorithm ◽  
Data Set ◽  
The World ◽  
Long Time ◽  
Life Threatening ◽  
Health Organization ◽  
Logistic Regression Algorithm ◽  
Asymptomatic Phase

Diabetes is one of the fastest-growing, life-threatening, chronic degenerative diseases. According to the World Health Organization (WHO), it has affected 422 million people worldwide in 2018. Approximately 50% of all people who suffer diabetes are not diagnosed due to the asymptomatic phase which usually lasts a long time. In this work, a data set of 520 instances has been used. The data set has been analyzed with the next three algorithms: logistic regression algorithm, decision trees and random forest. The results show that the decision tree algorithm had better performance with an AUC of 98%. Also, it was found the most common symptoms that a person with a risk of diabetes presents are polyuria, polydipsia and sudden weight loss.

Destabilization of Alzheimer’s Aβ42 protofibrils with acyclovir, carmustine, curcumin, and tetracycline: Insights from molecular dynamics simulations

2021 ◽  
Author(s):  
Ishrat Jahan ◽  
Shahid M Nayeem
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Neurodegenerative Diseases ◽  
Molecular Dynamics Simulations ◽  
Amyloid Β ◽  
Neural Tissue ◽  
Amyloid Β Peptide ◽  
Characteristic Symptom ◽  
Dynamics Simulations

One of the most common dementia among neurodegenerative diseases is Alzheimer’s disease (AD). The characteristic symptom of AD is the deposition and aggregation of amyloid-β-peptide in the neural tissue. A...

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