scholarly journals Cold Atmospheric Plasma Modification of Amyloid β

2021 ◽  
Vol 22 (6) ◽  
pp. 3116
Author(s):  
Maho Yagi-Utsumi ◽  
Tomohiro Tanaka ◽  
Yoko Otsubo ◽  
Akira Yamashita ◽  
Shinji Yoshimura ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Protein Structures ◽  
Amyloid Β ◽  
Atmospheric Plasma ◽  
Plasma Modification ◽  
Resonance Spectroscopy ◽  
Amyloid Formation ◽  
Cold Atmospheric Plasma ◽  
Methionine Residue ◽  
Aβ Amyloid

Cold atmospheric plasma (CAP) has attracted much attention in the fields of biotechnology and medicine owing to its potential utility in clinical applications. Recently accumulating evidence has demonstrated that CAP influences protein structures. However, there remain open questions regarding the molecular mechanisms behind the CAP-induced structural perturbations of biomacromolecules. Here, we investigated the potential effects of CAP irradiation of amyloid β (Aβ), an amyloidogenic protein associated with Alzheimer’s disease. Using nuclear magnetic resonance spectroscopy, we observed gradual spectral changes in Aβ after a 10 s CAP pretreatment, which also suppressed its fibril formation, as revealed by thioflavin T assay. As per mass spectrometric analyses, these effects were attributed to selective oxidation of the methionine residue (Met) at position 35. Interestingly, this modification occurred when Aβ was dissolved into a pre-irradiated buffer, indicating that some reactive species oxidize the Met residue. Our results strongly suggest that the H2O2 generated in the solution by CAP irradiation is responsible for Met oxidation, which inhibits Aβ amyloid formation. The findings of the present study provide fundamental insights into plasma biology, giving clues for developing novel applications of CAP.

scholarly journals Sp1 and Smad transcription factors co-operate to mediate TGF-β-dependent activation of amyloid-β precursor protein gene transcription

2004 ◽  
Vol 383 (2) ◽  
pp. 393-399 ◽  
Author(s):  
Fabian DOCAGNE ◽  
Cecilia GABRIEL ◽  
Nathalie LEBEURRIER ◽  
Sylvain LESNÉ ◽  
Yannick HOMMET ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Amyloid Β ◽  
Transforming Growth Factor Β ◽  
Precursor Protein ◽  
Transcriptional Level ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid

Abnormal deposition of Aβ (amyloid-β peptide) is one of the hallmarks of AD (Alzheimer's disease). This peptide results from the processing and cleavage of its precursor protein, APP (amyloid-β precursor protein). We have demonstrated previously that TGF-β (transforming growth factor-β), which is overexpressed in AD patients, is capable of enhancing the synthesis of APP by astrocytes by a transcriptional mechanism leading to the accumulation of Aβ. In the present study, we aimed at further characterization of the molecular mechanisms sustaining this TGF-β-dependent transcriptional activity. We report the following findings: first, TGF-β is capable of inducing the transcriptional activity of a reporter gene construct corresponding to the +54/+74 region of the APP promoter, named APPTRE (APP TGF-β-responsive element); secondly, although this effect is mediated by a transduction pathway involving Smad3 (signalling mother against decapentaplegic peptide 3) and Smad4, Smad2 or other Smads failed to induce the activity of APPTRE. We also observed that the APPTRE sequence not only responds to the Smad3 transcription factor, but also the Sp1 (signal protein 1) transcription factor co-operates with Smads to potentiate the TGF-β-dependent activation of APP. TGF-β signalling induces the formation of nuclear complexes composed of Sp1, Smad3 and Smad4. Overall, the present study gives new insights for a better understanding of the fine molecular mechanisms occurring at the transcriptional level and regulating TGF-β-dependent transcription. In the context of AD, our results provide additional evidence for a key role for TGF-β in the regulation of Aβ production.

scholarly journals Structure and Aggregation Mechanisms in Amyloids

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1195 ◽  
Author(s):  
Zaida L. Almeida ◽  
Rui M. M. Brito
Keyword(s):  
Molecular Species ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Current Knowledge ◽  
Point Of View ◽  
Resonance Spectroscopy ◽  
Amyloid Formation ◽  
Amyloid Fibril Formation ◽  
Misfolding Diseases ◽  
Amyloid Cascade

The aggregation of a polypeptide chain into amyloid fibrils and their accumulation and deposition into insoluble plaques and intracellular inclusions is the hallmark of several misfolding diseases known as amyloidoses. Alzheimer′s, Parkinson′s and Huntington’s diseases are some of the approximately 50 amyloid diseases described to date. The identification and characterization of the molecular species critical for amyloid formation and disease development have been the focus of intense scrutiny. Methods such as X-ray and electron diffraction, solid-state nuclear magnetic resonance spectroscopy (ssNMR) and cryo-electron microscopy (cryo-EM) have been extensively used and they have contributed to shed a new light onto the structure of amyloid, revealing a multiplicity of polymorphic structures that generally fit the cross-β amyloid motif. The development of rational therapeutic approaches against these debilitating and increasingly frequent misfolding diseases requires a thorough understanding of the molecular mechanisms underlying the amyloid cascade. Here, we review the current knowledge on amyloid fibril formation for several proteins and peptides from a kinetic and thermodynamic point of view, the structure of the molecular species involved in the amyloidogenic process, and the origin of their cytotoxicity.

scholarly journals Cold Atmospheric Plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gillian E. Conway ◽  
Zhonglei He ◽  
Ana Lacramioara Hutanu ◽  
George Paul Cribaro ◽  
Eline Manaloto ◽  
...  
Keyword(s):  
Cell Death ◽  
Glioblastoma Multiforme ◽  
Plasma Treatment ◽  
Acridine Orange ◽  
Molecular Mechanisms ◽  
Confocal Imaging ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma ◽  
Rapid Accumulation ◽  
Lysosomal Accumulation

Abstract Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma treated cells that stained positive with acridine orange. Western immunoblotting confirmed that autophagy is not activated following plasma treatment. Acridine orange intensity correlates closely with the lysosomal marker Lyso TrackerTM Deep Red. Further investigation using isosurface visualisation of confocal imaging confirmed that lysosomal accumulation occurs in plasma treated cells. The accumulation of lysosomes was associated with concomitant cell death following plasma treatment. In conclusion, we observed rapid accumulation of acidic vesicles and cell death following CAP treatment in GBM cells. We found no evidence that either apoptosis or autophagy, however, determined that a rapid accumulation of late stage endosomes/lysosomes precedes membrane permeabilisation, mitochondrial membrane depolarisation and caspase independent cell death.

Structural origin of polymorphism of Alzheimer's amyloid β-fibrils

2012 ◽  
Vol 447 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Audrey Agopian ◽  
Zhefeng Guo
Keyword(s):  
Amyloid Fibrils ◽  
Spin Exchange ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Side Chain ◽  
Resonance Spectroscopy ◽  
Amyloid Β Peptide ◽  
Amyloid Proteins ◽  
Aβ Amyloid

Formation of senile plaques containing amyloid fibrils of Aβ (amyloid β-peptide) is a pathological hallmark of Alzheimer's disease. Unlike globular proteins, which fold into unique structures, the fibrils of Aβ and other amyloid proteins often contain multiple polymorphs. Polymorphism of amyloid fibrils leads to different toxicity in amyloid diseases and may be the basis for prion strains, but the structural origin for fibril polymorphism is still elusive. In the present study we investigate the structural origin of two major fibril polymorphs of Aβ40: an untwisted polymorph formed under agitated conditions and a twisted polymorph formed under quiescent conditions. Using electron paramagnetic resonance spectroscopy, we studied the inter-strand side-chain interactions at 14 spin-labelled positions in the Aβ40 sequence. The results of the present study show that the agitated fibrils have stronger inter-strand spin–spin interactions at most of the residue positions investigated. The two hydrophobic regions at residues 17–20 and 31–36 have the strongest interactions in agitated fibrils. Distance estimates on the basis of the spin exchange frequencies suggest that inter-strand distances at residues 17, 20, 32, 34 and 36 in agitated fibrils are approximately 0.2 Å (1 Å=0.1 nm) closer than in quiescent fibrils. We propose that the strength of inter-strand side-chain interactions determines the degree of β-sheet twist, which then leads to the different association patterns between different cross β-units and thus distinct fibril morphologies. Therefore the inter-strand side-chain interaction may be a structural origin for fibril polymorphism in Aβ and other amyloid proteins.

Impairment of the activity of the plasma membrane Ca2+-ATPase in Alzheimer's disease

2011 ◽  
Vol 39 (3) ◽  
pp. 819-822 ◽  
Author(s):  
Ana M. Mata ◽  
María Berrocal ◽  
M. Rosario Sepúlveda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid

AD (Alzheimer's disease) is an age-associated neurodegenerative disorder where the accumulation of neurotoxic Aβ (amyloid β-peptide) in senile plaques is a typical feature. Recent studies point out a relationship between Aβ neurotoxicity and Ca2+ dyshomoeostasis, but the molecular mechanisms involved are still under discussion. The PMCAs (plasma membrane Ca2+-ATPases) are a multi-isoform family of proteins highly expressed in brain that is implicated in the maintenance of low intraneural Ca2+ concentration. Therefore the malfunction of this pump may also be responsible for Ca2+ homoeostasis failure in AD. We have found that the Ca2+-dependence of PMCA activity is affected in human brains diagnosed with AD, being related to the enrichment of Aβ. The peptide produces an inhibitory effect on the activity of PMCA which is isoform-specific, with the greatest inhibition of PMCA4. Besides, cholesterol blocked the inhibitory effect of Aβ, which is consistent with the lack of any Aβ effect on PMCA4 found in cholesterol-enriched lipid rafts isolated from pig brain. These observations suggest that PMCAs are a functional component of the machinery that leads to Ca2+ dysregulation in AD and propose cholesterol enrichment in rafts as a protector of the Aβ-mediated inhibition on PMCA.

scholarly journals Cold Atmospheric Plasma Cancer Treatment, a Critical Review

2021 ◽  
Vol 11 (16) ◽  
pp. 7757
Author(s):  
Dayun Yan ◽  
Alisa Malyavko ◽  
Qihui Wang ◽  
Li Lin ◽  
Jonathan H. Sherman ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Critical Evaluation ◽  
Atmospheric Plasma ◽  
Physical Factors ◽  
Atmospheric Conditions ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Biological Impacts ◽  
Indirect Treatment

Cold atmospheric plasma (CAP) is an ionized gas, the product of a non-equilibrium discharge at atmospheric conditions. Both chemical and physical factors in CAP have been demonstrated to have unique biological impacts in cancer treatment. From a chemical-based perspective, the anti-cancer efficacy is determined by the cellular sensitivity to reactive species. CAP may also be used as a powerful anti-cancer modality based on its physical factors, mainly EM emission. Here, we delve into three CAP cancer treatment approaches, chemically based direct/indirect treatment and physical-based treatment by discussing their basic principles, features, advantages, and drawbacks. This review does not focus on the molecular mechanisms, which have been widely introduced in previous reviews. Based on these approaches and novel adaptive plasma concepts, we discuss the potential clinical application of CAP cancer treatment using a critical evaluation and forward-looking perspectives.

Ca2+ enhances Aβ polymerization rate and fibrillar stability in a dynamic manner

2013 ◽  
Vol 450 (1) ◽  
pp. 189-197 ◽  
Author(s):  
Kristoffer Brännström ◽  
Anders Öhman ◽  
Malin Lindhagen-Persson ◽  
Anders Olofsson
Keyword(s):  
Self Assembly ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Mechanistic Explanation ◽  
Elongation Rate ◽  
Polymerization Rate ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid ◽  
Ad Alzheimer’S Disease

Identifying factors that affect the self-assembly of Aβ (amyloid-β peptide) is of utmost importance in the quest to understand the molecular mechanisms causing AD (Alzheimer's disease). Ca2+ has previously been shown to accelerate both Aβ fibril nucleation and maturation, and dysregulated Ca2+ homoeostasis frequently correlates with development of AD. The mechanisms regarding Ca2+ binding, as well as its effect on fibril kinetics, are not fully understood. Using a polymerization assay we show that Ca2+ in a dynamic and reversible manner enhances both the elongation rate and fibrillar stability, where specifically the ‘dock and lock’ phase mechanism is enhanced. Through NMR analysis we found that Ca2+ affects the fibrillar architecture. In addition, and unexpectedly, we found that Ca2+ does not bind the free Aβ monomer. This implies that Ca2+ binding requires an architecture adopted by assembled peptides, and consequently is mediated through intermolecular interactions between adjacent peptides. This gives a mechanistic explanation to the enhancing effect on fibril maturation and indicates structural similarities between prefibrillar structures and mature amyloid. Taken together we show how Ca2+ levels affect the delicate equilibrium between the monomeric and assembled Aβ and how fluctuations in vivo may contribute to development and progression of the disease.

Mechanisms of memory loss in Aβ and tau mouse models

2005 ◽  
Vol 33 (4) ◽  
pp. 591-594 ◽  
Author(s):  
K.H. Ashe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Memory Loss ◽  
Amyloid Β ◽  
Aβ Amyloid ◽  
Mechanisms Of Memory

Although memory loss is the central symptom of Alzheimer's disease, the pathophysiological mechanisms leading to dementia are poorly understood. It is difficult to answer this issue with studies in humans and impossible in cultured cells. Therefore animal models are needed to elucidate the molecular mechanisms leading to dementia. The chief neuropathological changes during Alzheimer's disease, namely neurofibrillary tangles and amyloid plaques, have helped us to determine which molecules to focus upon in the animal models, specifically Aβ (amyloid β) and tau. This paper presents my perspective on what we have learnt about mechanisms of memory loss from Aβ and tau mouse models of Alzheimer's disease.

Cold atmospheric plasma modification of curcumin loaded in tri‐phosphate chitosan nanoparticles enhanced breast cancer cells apoptosis

2020 ◽  
Vol 32 (1) ◽  
pp. 31-40
Author(s):  
Azadeh Sadoughi ◽  
Shiva Irani ◽  
Shadab Bagheri‐Khoulenjani ◽  
Seyed Mohammad Atyabi ◽  
Nafiseh Olov
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chitosan Nanoparticles ◽  
Atmospheric Plasma ◽  
Plasma Modification ◽  
Cold Atmospheric Plasma

scholarly journals Amyloid-Mediated Mechanisms of Membrane Disruption

Biophysica ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 137-156
Author(s):  
Michele F. M. Sciacca ◽  
Carmelo La Rosa ◽  
Danilo Milardi
Keyword(s):  
Self Assembly ◽  
Molecular Mechanisms ◽  
Conformational Transition ◽  
Prion Diseases ◽  
Membrane Damage ◽  
Amyloid Β ◽  
Amyloid Formation ◽  
Islet Amyloid ◽  
Amyloid Aggregates ◽  
Abnormal Accumulation

Protein aggregation and amyloid formation are pathogenic events underlying the development of an increasingly large number of human diseases named “proteinopathies”. Abnormal accumulation in affected tissues of amyloid β (Aβ) peptide, islet amyloid polypeptide (IAPP), and the prion protein, to mention a few, are involved in the occurrence of Alzheimer’s (AD), type 2 diabetes mellitus (T2DM) and prion diseases, respectively. Many reports suggest that the toxic properties of amyloid aggregates are correlated with their ability to damage cell membranes. However, the molecular mechanisms causing toxic amyloid/membrane interactions are still far to be completely elucidated. This review aims at describing the mutual relationships linking abnormal protein conformational transition and self-assembly into amyloid aggregates with membrane damage. A cross-correlated analysis of all these closely intertwined factors is thought to provide valuable insights for a comprehensive molecular description of amyloid diseases and, in turn, the design of effective therapies.

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