Special Issue "Protein Folding, Aggregation, and Cell Death"

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cell Biology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 13384

Special Issue Editors

Dr. Katsuya Iuchi
E-Mail Website
Guest Editor
Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, 3-3-1 Kichijojikitamachi, Musashino-shi, Tokyo 180-8633, Japan
Interests: cell death; apoptosis; necrosis; mitochondria; lipid peroxidation
Dr. Young-Ho Lee
E-Mail Website
Guest Editor
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Ochang, Cheongju, Chungbuk 28199, Korea
Interests: protein misfolding and aggregation; protein structure/dynamics/stability; thermodynamics
Dr. Masaki Okumura
E-Mail Website
Guest Editor
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8578, Japan
Interests: oxidative folding; chaperone; ER stress; protein homeostasis; LLPS

Special Issue Information

The protein homeostasis system, including autophagy, chaperone, and unfolded protein response, is one of the most essential gatekeepers to maintain cell homeostasis. Thus, the loss of protein homeostasis due to protein misfolding and aggregation often results in cell death with gain-of-toxic function and loss-of-function diseases such as neurodegenerative and many other aging-related disorders. Key and fundamental properties of protein (mis)folding and aggregation in causing cell death have been increasing revealed. However, a clearer understanding of the complex mechanisms of protein misfolding diseases remains elusive. This Special Issue focuses on in vitro and in vivo studies of protein folding, aggregation, and cell death.

Dear Colleagues,

Proteins are one of the most fundamental players for numerous biological processes that sustain living organisms. The correct folding of nascent polypeptides from unstructured conformations to the native structure in cells is a prerequisite for gain-of-function of proteins. Stochastic and environment-induced misfolding often results in irreversible protein aggregation, which causes loss-of-function and gain-of-toxic-function of proteins by damaging organelles and inducing cell death.

The protein homeostasis (proteostasis) system, including autophagy, unfolded protein response, and chaperone function, is fundamental to keep cell homeostasis. Among them, chaperone plays a central role for protein homeostasis by helping correct folding and preventing aggregation of misfolded proteins. Most seriously, errors in the proteostasis system in organelles, cells, tissues, and organs give rise to various protein misfolding diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), type 2 diabetes mellitus (T2DM), and amyotrophic lateral sclerosis (ALS). Misfolded and aggregated proteins interact with distinct cellular membranes, e.g., the plasma and organelle membranes, which affects the regulation of organelle function and intracellular signaling associated with apoptotic and non-apoptotic cell death processes. In addition, the interaction of mis-regulated protein aggregates with cellular organelles such as the mitochondria and endoplasmic reticulum has shown the loss of cellular calcium homeostasis with oxidative stress, thereby leading to several types of protein misfolding diseases.

Although several key and underlying aspects of protein folding, misfolding-induced aggregation, chaperone function, and their relation to cell death have been suggested, complicated linkages among these biological and pathological processes remain to be further discussed. In order to gain a deeper understanding, we invite cutting-edge researchers to submit original and review articles on the broad topic of “Protein Folding, Aggregation, and Cell Death”. This Special Issue will collect comprehensive manuscripts and provide valuable insight for the scientific community, ranging from basic to clinical researchers. Original research articles, timely reviews, and short communications are welcome.

Dr. Katsuya Iuchi

Dr. Young-Ho Lee

Dr. Masaki Okumura

Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Amyloid fibril
  • Apoptotic cell death
  • Calcium homeostasis
  • Endoplasmic reticulum
  • Lipid membrane
  • Mitochondria
  • Non-apoptotic cell death
  • Organelle dysfunction
  • Oxidative stress
  • Protein aggregation
  • Protein folding
  • Protein misfolding disease

Published Papers (13 papers)

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Research

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Article
Computational Insights into the Unfolding of a Destabilized Superoxide Dismutase 1 Mutant
Biology 2021, 10(12), 1240; https://doi.org/10.3390/biology10121240 - 27 Nov 2021
Viewed by 601
Abstract
In this work, we investigate the β-barrel of superoxide dismutase 1 (SOD1) in a mutated form, the isoleucine 35 to alanine (I35A) mutant, commonly used as a model system to decipher the role of the full-length apoSOD1 protein in amyotrophic lateral sclerosis [...] Read more.
In this work, we investigate the β-barrel of superoxide dismutase 1 (SOD1) in a mutated form, the isoleucine 35 to alanine (I35A) mutant, commonly used as a model system to decipher the role of the full-length apoSOD1 protein in amyotrophic lateral sclerosis (ALS). It is known from experiments that the mutation reduces the stability of the SOD1 barrel and makes it largely unfolded in the cell at 37 degrees Celsius. We deploy state-of-the-art computational machinery to examine the thermal destabilization of the I35A mutant by comparing two widely used force fields, Amber a99SB-disp and CHARMM36m. We find that only the latter force field, when combined with the Replica Exchange with Solute Scaling (REST2) approach, reproduces semi-quantitatively the experimentally observed shift in the melting between the original and the mutated SOD1 barrel. In addition, we analyze the unfolding process and the conformational landscape of the mutant, finding these largely similar to those of the wildtype. Nevertheless, we detect an increased presence of partially misfolded states at ambient temperatures. These states, featuring conformational changes in the region of the β-strands β4β6, might provide a pathway for nonnative aggregation. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Article
Pathogenic D76N Variant of β2-Microglobulin: Synergy of Diverse Effects in Both the Native and Amyloid States
Biology 2021, 10(11), 1197; https://doi.org/10.3390/biology10111197 - 17 Nov 2021
Viewed by 829
Abstract
β2-microglobulin (β2m), the light chain of the MHC-I complex, is associated with dialysis-related amyloidosis (DRA). Recently, a hereditary systemic amyloidosis was discovered, caused by a naturally occurring D76N β2m variant, which showed a structure remarkably similar to the wild-type (WT) protein, [...] Read more.
β2-microglobulin (β2m), the light chain of the MHC-I complex, is associated with dialysis-related amyloidosis (DRA). Recently, a hereditary systemic amyloidosis was discovered, caused by a naturally occurring D76N β2m variant, which showed a structure remarkably similar to the wild-type (WT) protein, albeit with decreased thermodynamic stability and increased amyloidogenicity. Here, we investigated the role of the D76N mutation in the amyloid formation of β2m by point mutations affecting the Asp76-Lys41 ion-pair of WT β2m and the charge cluster on Asp38. Using a variety of biophysical techniques, we investigated the conformational stability and partial unfolding of the native state of the variants, as well as their amyloidogenic propensity and the stability of amyloid fibrils under various conditions. Furthermore, we studied the intermolecular interactions of WT and mutant proteins with various binding partners that might have in vivo relevance. We found that, relative to WT β2m, the exceptional amyloidogenicity of the pathogenic D76N β2m variant is realized by the deleterious synergy of diverse effects of destabilized native structure, higher sensitivity to negatively charged amphiphilic molecules (e.g., lipids) and polyphosphate, more effective fibril nucleation, higher conformational stability of fibrils, and elevated affinity for extracellular components, including extracellular matrix proteins. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Article
Molecular Effects of Elongation Factor Ts and Trigger Factor on the Unfolding and Aggregation of Elongation Factor Tu Induced by the Prokaryotic Molecular Chaperone Hsp33
Biology 2021, 10(11), 1171; https://doi.org/10.3390/biology10111171 - 12 Nov 2021
Viewed by 576
Abstract
Hsp33, a prokaryotic redox-regulated holding chaperone, has been recently identified to be able to exhibit an unfoldase and aggregase activity against elongation factor Tu (EF-Tu) in its reduced state. In this study, we investigated the effect of elongation factor Ts (EF-Ts) and trigger [...] Read more.
Hsp33, a prokaryotic redox-regulated holding chaperone, has been recently identified to be able to exhibit an unfoldase and aggregase activity against elongation factor Tu (EF-Tu) in its reduced state. In this study, we investigated the effect of elongation factor Ts (EF-Ts) and trigger factor (TF) on Hsp33-mediated EF-Tu unfolding and aggregation using gel filtration, light scattering, circular dichroism, and isothermal titration calorimetry. We found that EF-Tu unfolding and subsequent aggregation induced by Hsp33 were evident even in its complex state with EF-Ts, which enhanced EF-Tu stability. In addition, although TF alone had no substantial effect on the stability of EF-Tu, it markedly amplified the Hsp33-mediated EF-Tu unfolding and aggregation. Collectively, the present results constitute the first example of synergistic unfoldase/aggregase activity of molecular chaperones and suggest that the stability of EF-Tu is modulated by a sophisticated network of molecular chaperones to regulate protein biosynthesis in cells under stress conditions. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Article
Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding
Biology 2021, 10(11), 1112; https://doi.org/10.3390/biology10111112 - 28 Oct 2021
Viewed by 801
Abstract
P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured [...] Read more.
P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured cells, but it remains unclear whether complex formation between P5 and other PDIs is involved in regulating enzymatic and chaperone functions. Herein, we established the far-western blot method to detect non-covalent interactions between P5 and other PDIs and found that PDI and ERp72 are partner proteins of P5. The enzymatic activity of P5-mediated oxidative folding is up-regulated by PDI, while the chaperone activity of P5 is stimulated by ERp72. These findings shed light on the mechanism by which the complex formations among PDIs drive to synergistically accelerate protein folding and prevents aggregation. This knowledge has implications for understanding misfolding-related pathology. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Article
Zinc-Dependent Oligomerization of Thermus thermophilus Trigger Factor Chaperone
Biology 2021, 10(11), 1106; https://doi.org/10.3390/biology10111106 - 26 Oct 2021
Cited by 1 | Viewed by 785
Abstract
Thermus thermophilus trigger factor (TtTF) is a zinc-dependent molecular chaperone whose folding-arrest activity is regulated by Zn2+. However, little is known about the mechanism of zinc-dependent regulation of the TtTF activity. Here we exploit in vitro biophysical experiments [...] Read more.
Thermus thermophilus trigger factor (TtTF) is a zinc-dependent molecular chaperone whose folding-arrest activity is regulated by Zn2+. However, little is known about the mechanism of zinc-dependent regulation of the TtTF activity. Here we exploit in vitro biophysical experiments to investigate zinc-binding, the oligomeric state, the secondary structure, and the thermal stability of TtTF in the absence and presence of Zn2+. The data show that full-length TtTF binds Zn2+, but the isolated domains and tandem domains of TtTF do not bind to Zn2+. Furthermore, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra suggested that Zn2+-binding induces the partial structural changes of TtTF, and size exclusion chromatography-multi-angle light scattering (SEC-MALS) showed that Zn2+ promotes TtTF oligomerization. Given the previous work showing that the activity regulation of E. coli trigger factor is accompanied by oligomerization, the data suggest that TtTF exploits zinc ions to induce the structural change coupled with the oligomerization to assemble the client-binding site, thereby effectively preventing proteins from misfolding in the thermal environment. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Article
Abnormal Enhancement of Protein Disulfide Isomerase-like Activity of a Cyclic Diselenide Conjugated with a Basic Amino Acid by Inserting a Glycine Spacer
Biology 2021, 10(11), 1090; https://doi.org/10.3390/biology10111090 - 24 Oct 2021
Viewed by 557
Abstract
In a previous study, we reported that (S)-1,2-diselenane-4-amine (1) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amide bond [...] Read more.
In a previous study, we reported that (S)-1,2-diselenane-4-amine (1) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amide bond improves the catalytic activity of 1 by increasing its diselenide (Se–Se) reduction potential (E′°). In this study, to modulate the Se–Se redox properties and the association of the compounds with a protein substrate, new catalysts, in which a Gly spacer was inserted between 1 and Xaa, were synthesized. Exhaustive comparison of the PDI-like catalytic activities and E′° values among 1, 1-Xaa, and 1-Gly-Xaa showed that the insertion of a Gly spacer into 1-Xaa either did not change or slightly reduced the PDI-like activity and the E′° values. Importantly, however, only 1-Gly-Arg deviated from this generality and showed obviously increased E°′ value and PDI-like activity compared to the corresponding compound with no Gly spacer (1-Arg); on the contrary, its catalytic activity was the highest among the diselenide compounds employed in this study, while this abnormal enhancement of the catalytic activity of 1-Gly-Arg could not be fully explained by the thermodynamics of the Se–Se bond and its association ability with protein substrates. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Article
Idebenone Decreases Aβ Pathology by Modulating RAGE/Caspase-3 Signaling and the Aβ Degradation Enzyme NEP in a Mouse Model of AD
Biology 2021, 10(9), 938; https://doi.org/10.3390/biology10090938 - 19 Sep 2021
Cited by 3 | Viewed by 851
Abstract
The coenzyme Q10 analogue idebenone is an FDA-approved antioxidant that can cross the blood–brain barrier (BBB). The effects of idebenone on the pathology of Alzheimer’s disease (AD) and the underlying molecular mechanisms have not been comprehensively investigated. Here, we examined the impact of [...] Read more.
The coenzyme Q10 analogue idebenone is an FDA-approved antioxidant that can cross the blood–brain barrier (BBB). The effects of idebenone on the pathology of Alzheimer’s disease (AD) and the underlying molecular mechanisms have not been comprehensively investigated. Here, we examined the impact of idebenone treatment on AD pathology in 5xFAD mice, a model of AD. Idebenone significantly downregulated Aβ plaque number via multi-directional pathways in this model. Specifically, idebenone reduced the RAGE/caspase-3 signaling pathway and increased levels of the Aβ degradation enzyme NEP and α-secretase ADAM17 in 5xFAD mice. Importantly, idebenone significantly suppressed tau kinase p-GSK3βY216 levels, thereby inhibiting tau hyperphosphorylation at Thr231 and total tau levels in 5xFAD mice. Taken together, the present study indicates that idebenone modulates amyloidopathy and tauopathy in 5xFAD mice, suggesting therapeutic potential for AD. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Article
The Function of Drosophila USP14 in Endoplasmic Reticulum Stress and Retinal Degeneration in a Model for Autosomal Dominant Retinitis Pigmentosa
Biology 2020, 9(10), 332; https://doi.org/10.3390/biology9100332 - 12 Oct 2020
Viewed by 1424
Abstract
Endoplasmic reticulum (ER) stress and its adaptive cellular response, the unfolded protein response (UPR), are involved in various diseases including neurodegenerative diseases, metabolic diseases, and even cancers. Here, we analyzed the novel function of ubiquitin-specific peptidase 14 (USP14) in ER stress. The overexpression [...] Read more.
Endoplasmic reticulum (ER) stress and its adaptive cellular response, the unfolded protein response (UPR), are involved in various diseases including neurodegenerative diseases, metabolic diseases, and even cancers. Here, we analyzed the novel function of ubiquitin-specific peptidase 14 (USP14) in ER stress. The overexpression of Drosophila USP14 protected the cells from ER stress without affecting the proteasomal activity. Null Hong Kong (NHK) and alpha-1-antitrypsin Z (ATZ) are ER-associated degradation substrates. The degradation of NHK, but not of ATZ, was delayed by USP14. USP14 restored the levels of rhodopsin-1 protein in a Drosophila model for autosomal dominant retinitis pigmentosa and suppressed the retinal degeneration in this model. In addition, we observed that proteasome complex is dynamically reorganized in response to ER stress in human 293T cells. These findings suggest that USP14 may be a therapeutic strategy in diseases associated with ER stress. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Review

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Review
Oligomannose-Type Glycan Processing in the Endoplasmic Reticulum and Its Importance in Misfolding Diseases
Biology 2022, 11(2), 199; https://doi.org/10.3390/biology11020199 - 27 Jan 2022
Viewed by 693
Abstract
Glycoprotein folding plays a critical role in sorting glycoprotein secretion and degradation in the endoplasmic reticulum (ER). Furthermore, relationships between glycoprotein folding and several diseases, such as type 2 diabetes and various neurodegenerative disorders, are indicated. Patients’ cells with type 2 diabetes, and [...] Read more.
Glycoprotein folding plays a critical role in sorting glycoprotein secretion and degradation in the endoplasmic reticulum (ER). Furthermore, relationships between glycoprotein folding and several diseases, such as type 2 diabetes and various neurodegenerative disorders, are indicated. Patients’ cells with type 2 diabetes, and various neurodegenerative disorders induce ER stress, against which the cells utilize the unfolded protein response for protection. However, in some cases, chronic and/or massive ER stress causes critical damage to cells, leading to the onset of ER stress-related diseases, which are categorized into misfolding diseases. Accumulation of misfolded proteins may be a cause of ER stress, in this respect, perturbation of oligomannose-type glycan processing in the ER may occur. A great number of studies indicate the relationships between ER stress and misfolding diseases, while little evidence has been reported on the connection between oligomannose-type glycan processing and misfolding diseases. In this review, we summarize alteration of oligomannose-type glycan processing in several ER stress-related diseases, especially misfolding diseases and show the possibility of these alteration of oligomannose-type glycan processing as indicators of diseases. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Review
Association between Sleep, Alzheimer’s, and Parkinson’s Disease
Biology 2021, 10(11), 1127; https://doi.org/10.3390/biology10111127 - 03 Nov 2021
Cited by 2 | Viewed by 1077
Abstract
The majority of neurodegenerative diseases are pathologically associated with protein misfolding and aggregation. Alzheimer’s disease (AD) is a type of dementia that slowly affects memory and cognitive function, and is characterized by the aggregation of the β-amyloid protein and tau neurofibrillary tangles in [...] Read more.
The majority of neurodegenerative diseases are pathologically associated with protein misfolding and aggregation. Alzheimer’s disease (AD) is a type of dementia that slowly affects memory and cognitive function, and is characterized by the aggregation of the β-amyloid protein and tau neurofibrillary tangles in the brain. Parkinson’s disease (PD) is a movement disorder typically resulting in rigidity and tremor, which is pathologically linked to the aggregation of α-synuclein, particularly in dopaminergic neurons in the midbrain. Sleep disorders commonly occur in AD and PD patients, and it can precede the onset of these diseases. For example, cognitively normal older individuals who have highly fragmented sleep had a 1.5-fold increased risk of subsequently developing AD. This suggests that sleep abnormalities may be a potential biomarker of these diseases. In this review, we describe the alterations of sleep in AD and PD, and discuss their potential in the early diagnosis of these diseases. We further discuss whether sleep disturbance could be a target for the treatment of these diseases. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Review
17O NMR Spectroscopy: A Novel Probe for Characterizing Protein Structure and Folding
Biology 2021, 10(6), 453; https://doi.org/10.3390/biology10060453 - 21 May 2021
Cited by 2 | Viewed by 995
Abstract
Oxygen is a key atom that maintains biomolecular structures, regulates various physiological processes, and mediates various biomolecular interactions. Oxygen-17 (17O), therefore, has been proposed as a useful probe that can provide detailed information about various physicochemical features of proteins. This is [...] Read more.
Oxygen is a key atom that maintains biomolecular structures, regulates various physiological processes, and mediates various biomolecular interactions. Oxygen-17 (17O), therefore, has been proposed as a useful probe that can provide detailed information about various physicochemical features of proteins. This is attributed to the facts that (1) 17O is an active isotope for nuclear magnetic resonance (NMR) spectroscopic approaches; (2) NMR spectroscopy is one of the most suitable tools for characterizing the structural and dynamical features of biomolecules under native-like conditions; and (3) oxygen atoms are frequently involved in essential hydrogen bonds for the structural and functional integrity of proteins or related biomolecules. Although 17O NMR spectroscopic investigations of biomolecules have been considerably hampered due to low natural abundance and the quadruple characteristics of the 17O nucleus, recent theoretical and technical developments have revolutionized this methodology to be optimally poised as a unique and widely applicable tool for determining protein structure and dynamics. In this review, we recapitulate recent developments in 17O NMR spectroscopy to characterize protein structure and folding. In addition, we discuss the highly promising advantages of this methodology over other techniques and explain why further technical and experimental advancements are highly desired. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Review
Cell Death via Lipid Peroxidation and Protein Aggregation Diseases
Biology 2021, 10(5), 399; https://doi.org/10.3390/biology10050399 - 04 May 2021
Cited by 5 | Viewed by 1417
Abstract
Lipid peroxidation of cellular membranes is a complicated cellular event, and it is both the cause and result of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, and atherosclerosis. Lipid peroxidation causes non-apoptotic cell death, which is associated with cell fate determination: survival [...] Read more.
Lipid peroxidation of cellular membranes is a complicated cellular event, and it is both the cause and result of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, and atherosclerosis. Lipid peroxidation causes non-apoptotic cell death, which is associated with cell fate determination: survival or cell death. During the radical chain reaction of lipid peroxidation, various oxidized lipid products accumulate in cells, followed by organelle dysfunction and the induction of non-apoptotic cell death. Highly reactive oxidized products from unsaturated fatty acids are detected under pathological conditions. Pathological protein aggregation is the general cause of these diseases. The cellular response to misfolded proteins is well-known as the unfolded protein response (UPR) and it is partially concomitant with the response to lipid peroxidation. Moreover, the association between protein aggregation and non-apoptotic cell death by lipid peroxidation is attracting attention. The link between lipid peroxidation and protein aggregation is a matter of concern in biomedical fields. Here, we focus on lethal protein aggregation in non-apoptotic cell death via lipid peroxidation. We reviewed the roles of protein aggregation in the initiation and execution of non-apoptotic cell death. We also considered the relationship between protein aggregation and oxidized lipid production. We provide an overview of non-apoptotic cell death with a focus on lipid peroxidation for therapeutic targeting during protein aggregation diseases. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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Review
Amyloids: The History of Toxicity and Functionality
Biology 2021, 10(5), 394; https://doi.org/10.3390/biology10050394 - 01 May 2021
Cited by 2 | Viewed by 1224
Abstract
Proteins can perform their specific function due to their molecular structure. Partial or complete unfolding of the polypeptide chain may lead to the misfolding and aggregation of proteins in turn, resulting in the formation of different structures such as amyloid aggregates. Amyloids are [...] Read more.
Proteins can perform their specific function due to their molecular structure. Partial or complete unfolding of the polypeptide chain may lead to the misfolding and aggregation of proteins in turn, resulting in the formation of different structures such as amyloid aggregates. Amyloids are rigid protein aggregates with the cross-β structure, resistant to most solvents and proteases. Because of their resistance to proteolysis, amyloid aggregates formed in the organism accumulate in tissues, promoting the development of various diseases called amyloidosis, for instance Alzheimer’s diseases (AD). According to the main hypothesis, it is considered that the cause of AD is the formation and accumulation of amyloid plaques of Aβ. That is why Aβ-amyloid is the most studied representative of amyloids. Therefore, in this review, special attention is paid to the history of Aβ-amyloid toxicity. We note the main problems with anti-amyloid therapy and write about new views on amyloids that can play positive roles in the different organisms including humans. Full article
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
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