Special Issue "Inflammation, Oxidative Stress and Protein Aggregation; Any Links?"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 October 2019).

Special Issue Editors

Prof. Dr. Eva Žerovnik
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Guest Editor
Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia
Interests: protein folding; protein aggregation; amyloid; Alzheimer’s disease; protein oligomers toxicity; autophagy; cystatins; stefin B
Special Issues and Collections in MDPI journals
Prof. Dr. Salvador Ventura
E-Mail Website
Guest Editor
Institute of Biotechnology and Biomedicine & Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Spain
Interests: protein folding; protein aggregation; protein design; high-throughput screening; bioinformatics; amyloids; Parkinson; nanomaterials; phase separation; prions; drug discovery
Special Issues and Collections in MDPI journals
Dr. Nataša Kopitar Jerala
E-Mail Website
Guest Editor
Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia
Interests: innate immune response; inflammasome; mitochondria; oxidative stress; proteinases and inhibitors
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammation is a complex immune response that enables survival during infection and maintains tissue homeostasis. In response to pathogens, damaged cells, or irritants a cascade of signals leads to the recruitment of immune cells. The sustained robust inflammation may lead to serious disorders due to the overproduction of pro-inflammatory cytokines and tissue damage. The proinflammatory cytokines IL-1β and IL-18 play a crucial role in tissue homeostasis. Their secretion is determined by the inflammasome, a multicomponent complex that processes IL-1β and IL-18 into mature cytokines. Reactive oxygen species (ROS) are implicated in inflammasome activation.

Proteostasis (proportion between the synthesis, translation, folding and degradation of proteins) should be in balance in a healthy cell, including neurons. However, due to different stressors among them, heat (fever, infection), acidification (lack or excess of nutrients) and oxidative stress, the mis-folding and aggregation of otherwise normal sequences of proteins occurs. Different chaperones, i.e., heat shock proteins, are turned on to deaggregate and restore the folding of proteins, however, the degradation and clearance from the cell by autophagy happen as a last resource. ROS can also increase upon protein aggregation, due to metals binding to the aggregates, membrane perturbation or permeabilization by soluble aggregates.

In this Special Issue we propose: 1) to discuss how oxidative stress influences the inflammatory immune response; 2) studies of the regulatory pathways, which are turned on in the cytosol to restore proteostasis; and 3) studies which shed light on the connections between different stressors and the amount of protein aggregates, and the localization of the smallest, still soluble aggregates (oligomers), which are supposed to be the most toxic.

Overall, by means of the proposed Special Issue, we expect to come closer to understanding the links between inflammatory response, oxidative stress and protein aggregation. Such knowledge may lead to common therapeutic targets to fight decreased proteostasis in aging or in neurodegenerative diseases.

Prof. Dr. Eva Žerovnik
Prof. Dr. Salvador Ventura
Dr. Nataša Kopitar Jerala
Guest Editors

Manuscript Submission Information

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Keywords

  • inflammation
  • cytokines IL-1β and IL-18
  • reactive oxygen species (ROS)
  • protein mis-folding
  • protein aggregation
  • amyloid
  • amyloid-beta peptide
  • neurodegeneration
  • signalling pathways
  • autophagy
  • mitochondrial damage

Published Papers (5 papers)

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Editorial

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Editorial
Special Issue: “Inflammation, Oxidative Stress and Protein Aggregation; Any Links?”
Cells 2020, 9(11), 2461; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9112461 - 11 Nov 2020
Viewed by 572
Abstract
Inflammation is a complex immune response that enables survival during infection and maintains tissue homeostasis [...] Full article
(This article belongs to the Special Issue Inflammation, Oxidative Stress and Protein Aggregation; Any Links?)
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Research

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Article
pH-Dependent Aggregation in Intrinsically Disordered Proteins Is Determined by Charge and Lipophilicity
Cells 2020, 9(1), 145; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9010145 - 08 Jan 2020
Cited by 14 | Viewed by 1830
Abstract
Protein aggregation is associated with an increasing number of human disorders and premature aging. Moreover, it is a central concern in the manufacturing of recombinant proteins for biotechnological and therapeutic applications. Nevertheless, the unique architecture of protein aggregates is also exploited by nature [...] Read more.
Protein aggregation is associated with an increasing number of human disorders and premature aging. Moreover, it is a central concern in the manufacturing of recombinant proteins for biotechnological and therapeutic applications. Nevertheless, the unique architecture of protein aggregates is also exploited by nature for functional purposes, from bacteria to humans. The relevance of this process in health and disease has boosted the interest in understanding and controlling aggregation, with the concomitant development of a myriad of algorithms aimed to predict aggregation propensities. However, most of these programs are blind to the protein environment and, in particular, to the influence of the pH. Here, we developed an empirical equation to model the pH-dependent aggregation of intrinsically disordered proteins (IDPs) based on the assumption that both the global protein charge and lipophilicity depend on the solution pH. Upon its parametrization with a model IDP, this simple phenomenological approach showed unprecedented accuracy in predicting the dependence of the aggregation of both pathogenic and functional amyloidogenic IDPs on the pH. The algorithm might be useful for diverse applications, from large-scale analysis of IDPs aggregation properties to the design of novel reversible nanofibrillar materials. Full article
(This article belongs to the Special Issue Inflammation, Oxidative Stress and Protein Aggregation; Any Links?)
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Article
Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages
Cells 2019, 8(12), 1476; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8121476 - 21 Nov 2019
Cited by 2 | Viewed by 1442
Abstract
Stefin B (cystatin B) is an intracellular inhibitor of cysteine cathepsins and mutations in the stefin B gene, resulting in the development of Unverricht–Lundborg disease, which is a form of myoclonic epilepsy. It was suggested that a key mechanism behind stefin B-mediated disease [...] Read more.
Stefin B (cystatin B) is an intracellular inhibitor of cysteine cathepsins and mutations in the stefin B gene, resulting in the development of Unverricht–Lundborg disease, which is a form of myoclonic epilepsy. It was suggested that a key mechanism behind stefin B-mediated disease progression was impaired redox homeostasis. Stefin B-deficient mice were found more sensitive to lipopolysaccharide (LPS)-induced sepsis as a consequence of increased expression of caspase-11 and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing (NLRP nflammasome activation and higher levels of mitochondrial reactive oxygen species (ROS). In the present study, we investigated if LPS-triggered oxidative stress affected the protein levels and redox status of redox sensitive proteins—thioredoxin, peroxiredoxins, and superoxide dismutases in macrophages and spleens of LPS-injected mice. LPS challenge was found to result in a marked elevation in mitochondrial peroxiredoxin 3 (Prx3), sulfiredoxin, and superoxide dismutase 2 (Sod2) in stefin B-deficient macrophages and spleens. We determined that sulfiredoxin is targeted to mitochondria after LPS challenge. In conclusion, the upregulation of mitochondrial redox-sensitive proteins Prx3 and Sod2 in stefin B-deficient cells implies a protective role of stefin B in mitochondrial function. Full article
(This article belongs to the Special Issue Inflammation, Oxidative Stress and Protein Aggregation; Any Links?)
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Article
Computational Assessment of Bacterial Protein Structures Indicates a Selection Against Aggregation
Cells 2019, 8(8), 856; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080856 - 08 Aug 2019
Cited by 5 | Viewed by 1329
Abstract
The aggregation of proteins compromises cell fitness, either because it titrates functional proteins into non-productive inclusions or because it results in the formation of toxic assemblies. Accordingly, computational proteome-wide analyses suggest that prevention of aggregation upon misfolding plays a key role in sequence [...] Read more.
The aggregation of proteins compromises cell fitness, either because it titrates functional proteins into non-productive inclusions or because it results in the formation of toxic assemblies. Accordingly, computational proteome-wide analyses suggest that prevention of aggregation upon misfolding plays a key role in sequence evolution. Most proteins spend their lifetimes in a folded state; therefore, it is conceivable that, in addition to sequences, protein structures would have also evolved to minimize the risk of aggregation in their natural environments. By exploiting the AGGRESCAN3D structure-based approach to predict the aggregation propensity of >600 Escherichia coli proteins, we show that the structural aggregation propensity of globular proteins is connected with their abundance, length, essentiality, subcellular location and quaternary structure. These data suggest that the avoidance of protein aggregation has contributed to shape the structural properties of proteins in bacterial cells. Full article
(This article belongs to the Special Issue Inflammation, Oxidative Stress and Protein Aggregation; Any Links?)
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Review

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Review
An Overview of Crucial Dietary Substances and Their Modes of Action for Prevention of Neurodegenerative Diseases
Cells 2020, 9(3), 576; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9030576 - 28 Feb 2020
Cited by 8 | Viewed by 1526
Abstract
Neurodegenerative diseases, namely Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis are becoming one of the main health concerns due to the increasing aging of the world’s population. These diseases often share the same biological mechanisms, including [...] Read more.
Neurodegenerative diseases, namely Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis are becoming one of the main health concerns due to the increasing aging of the world’s population. These diseases often share the same biological mechanisms, including neuroinflammation, oxidative stress, and/or protein fibrillation. Recently, there have been many studies published pointing out the possibilities to reduce and postpone the clinical manifestation of these deadly diseases through lifelong consumption of some crucial dietary substances, among which phytochemicals (e.g., polyphenols) and endogenous substances (e.g., acetyl-L-carnitine, coenzyme Q10, n-3 poysaturated fatty acids) showed the most promising results. Another important issue that has been pointed out recently is the availability of these substances to the central nervous system, where they have to be present in high enough concentrations in order to exhibit their neuroprotective properties. As so, such the aim of this review is to summarize the recent findings regarding neuroprotective substances, their mechanisms of action, as well as to point out therapeutic considerations, including their bioavailability and safety for humans. Full article
(This article belongs to the Special Issue Inflammation, Oxidative Stress and Protein Aggregation; Any Links?)
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