EditorialOxidative Stress, Chronic Inflammation, and Amyloidoses

Arkadiusz Orzechowski ,1 Anna Cywińska ,2 Agueda A. Rostagno ,3

and Federica M. Rizzi 4

1Department of Physiological Sciences, Warsaw University of Life Sciences (SGGW), Nowoursynowska 159, 02-776 Warsaw, Poland2Department of Pathology and Veterinary Diagnostics, Warsaw University of Life Sciences (SGGW), Nowoursynowska 159,02-776 Warsaw, Poland3Department of Pathology, New York University School of Medicine, 550 First Avenue, MSB 556, New York, NY 10016, USA4Dipartmento di Medicina a Chirurgia, Universita degli Studi di Parma, Via Volturno 39/E, Parma, Italy

Correspondence should be addressed to Arkadiusz Orzechowski; orzechowski_arkadiusz@wp.pl

Received 25 July 2019; Accepted 29 July 2019; Published 8 September 2019

Copyright © 2019 Arkadiusz Orzechowski et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Amyloid diseases are part of an emerging complex group ofchronic and progressive entities collectively known as disor-ders of protein folding. For reasons still under active investi-gation, soluble proteins normally found in interstitial orbiological fluids change their conformation and form poorlysoluble molecular assemblies that accumulate as extracellularfibrillar aggregates within the parenchyma and blood vesselsof different organs. Once formed, these amyloid fibrils thattypically exhibit a β-sheet-rich secondary structure are highlyresistant to proteolytic degradation, a characteristic thatimpairs their effective physiologic removal and leads to theirtissue accumulation inducing local hypoxia and cellular dam-age with overall organ dysfunction and, eventually, death.

The molecular pathogenic mechanisms associated withamyloid diseases are complex and involve cross-talk amongdifferent cell populations and cellular pathways. Mountingevidence points out to inflammation-related mechanismsand oxidative stress as associated burden for amyloidosis.In spite of multiple studies, it still remains to be elucidatedwhether oxidative stress is a key contributor to the diseasepathogenesis and progression or whether—on the contra-ry—it is a mere consequence of the cellular responses elicitedby the presence of amyloid deposits and the concomitantinflammatory processes affecting injured tissue. Thisspecial issue provides an updated view on the role of oxi-dative stress and inflammation-related cellular pathways tothe etiopathogenesis, progression, and treatment strategiesof amyloid diseases.

One of the papers of this special issue, “Hypoxia andInflammation as a Consequence of β-fibril Accumulation:A Perspective View for New Potential Therapeutic Targets,”addresses the link between local hypoxia and the inductionof chronic long-lasting inflammation in the context of the tis-sue accumulation of the β-sheet-rich amyloid deposits. Theauthors propose that the induction of cell death mechanismsin conjunction with local tissue hypoxia associated with theamyloid accumulation constitutes important events for thepathogenesis and progression of amyloidosis. The authorshypothesize that molecules released by necrotic cells acti-vate inflammatory responses through Damage-AssociatedMolecular Patterns (DAMPs) and evoke activation ofHIF-1α/NF-κB-dependent pathways suggesting that modu-lation of these cellular paths may constitute new therapeuticstrategies. Another manuscript of the special issue focuses onthe role of oxidative stress for the process of amyloidformation. The authors of “Suppression of Mouse AApoAIIAmyloidosis Progression by Daily Supplementation withOxidative Stress Inhibitors” examined the effect of the non-specific reactive oxygen species (ROS) scavenger tempoland the NADPH oxidase inhibitor apocynin on the processof amyloidogenesis using a mouse model of AApoAIIamyloidosis. Their results provide evidence that oxidativestress is involved in the progression of systemic amyloidosisbut indicate that, although oxidative stress inhibitors amelio-rated amyloid deposition, their use was unable to completelyblock the progression of amyloidosis. The paper entitled

HindawiOxidative Medicine and Cellular LongevityVolume 2019, Article ID 6024975, 2 pageshttps://doi.org/10.1155/2019/6024975

“High levels of β-Amyloid, Tau, and Phospho-Tau in RedBlood Cells as Biomarkers of Neuropathology in Senescence-Accelerated Mouse” describes a study conducted on theSenescence-Accelerated Mouse-Prone, SAMP8, a validatedmodel of Alzheimer’s disease (AD) with the aim of establish-ing novel sensitive disease biomarkers. The study illustratesthe increasing brain accumulation of amyloid-beta (Aβ) aswell as total and phosphorylated tau concomitant with theelevated levels of the inflammatory marker interleukin-1β.The brain accumulation kinetics parallels findings in redblood cells suggesting these proteins as putative peripheralAD biomarkers. The authors of the original manuscript“Syk and Hrs Regulate TLR3-Mediated Antiviral Responsein Murine Astrocytes” examined the regulation of the innateimmune response-related Toll-like receptor 3 (TLR3) signal-ing in the astrocytic cell line C8-D1A following stimulationwith a viral dsRNA mimetic (Pathogen-Associated Molecu-lar Patterns (PAMPs)). The study uncovers a relationshipbetween TLR3 and the endosomal sorting complex requiredfor transportation-0 (ESCRT-0), pointing out to the spleentyrosine kinase (Syk) as a dsRNA-activated kinase mediatingTLR3 signaling and the concomitant induction of IFNs andproinflammatory gene expression. The paper “Nitric OxideInfluences HSV-1-Induced Neuroinflammation,” aimed toelucidate the role of NO in neuroinflammation and neurode-generation based on the use of in vitro models of herpessimplex virus (HSV-1) infection of neuronal and glial cellcultures as well as intranasal viral infection of BALB/c mice.The authors describe a differential response to NO andHSV-1 infection for neuronal, microglial, and astrocytic cellsas well as in the concomitant production of IFN-alpha (IFN-α) and proinflammatory cytokines CXCL9 and CXCL10.Presented results help elucidate the molecular roles of NOand NO-related signaling during HSV-1-induced neuroin-flammation and neurodegeneration and indicate for thefirst time the existence of a link between Fas signalingdue to neuroinflammation and nitrosative stress duringHSV-1 infection.

Overall, the special issue highlights the contribution ofoxidative stress and chronic inflammation to the pathobiol-ogy of amyloid-associated diseases. The papers compiled inthis special issue widen the current knowledge of the molec-ular mechanisms involved in the etiology, progression, andaccumulation of β-sheet-enriched deposits in infectious andnoninfectious forms of amyloidosis.

Conflicts of Interest

The editors declare that there is no conflict of interest.

Arkadiusz OrzechowskiAnna Cywińska

Agueda A. RostagnoFederica M. Rizzi

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