Unfolding the Role of a Flavone-Based Fluorescent Antioxidant towards the Misfolding of Amyloid Proteins: An Endeavour to Probe Amyloid Aggregation

2020 ◽  
Vol 124 (49) ◽  
pp. 11133-11144
Author(s):  
Abhijit Karmakar ◽  
Tamanna Mallick ◽  
Chandrani Fouzder ◽  
Alpana Mukhuty ◽  
Samiran Mondal ◽  
...  
Keyword(s):  
Amyloid Aggregation ◽  
Amyloid Proteins

Role of the Structural Characteristics of Dendrimers in the Manifestation of the Antiamyloid Properties

INEOS OPEN ◽  
2020 ◽  
Vol 3 ◽  
Author(s):  
S. A. Sorokina ◽  
◽  
Yu. Yu. Stroilova ◽  
V. I. Muronets ◽  
Z. B. Shifrina ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Characteristics ◽  
Short Review ◽  
External Factors ◽  
Amyloid Aggregation ◽  
Amyloid Proteins ◽  
Molecular Parameters ◽  
Amyloid Aggregates ◽  
Aggregation Processes

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.

scholarly journals Implications of peptide assemblies in amyloid diseases

2017 ◽  
Vol 46 (21) ◽  
pp. 6492-6531 ◽  
Author(s):  
Pu Chun Ke ◽  
Marc-Antonie Sani ◽  
Feng Ding ◽  
Aleksandr Kakinen ◽  
Ibrahim Javed ◽  
...  
Keyword(s):  
Self Assembly ◽  
Amyloid Proteins ◽  
Amyloid Diseases

We highlight the role of molecular self-assembly in eliciting the mesoscopic and pathological properties of amyloid proteins. This knowledge is pivotal for the development of theranostics against amyloid diseases.

Role of Acetylcholinesterase in β-Amyloid Aggregation Studied by Accelerated Molecular Dynamics

2016 ◽  
Vol 7 (2) ◽  
pp. 396-402 ◽  
Author(s):  
Sofya V. Lushchekina ◽  
Ekaterina D. Kots ◽  
Dana A. Novichkova ◽  
Konstantin A. Petrov ◽  
Patrick Masson
Keyword(s):  
Molecular Dynamics ◽  
Amyloid Aggregation ◽  
Accelerated Molecular Dynamics ◽  
Β Amyloid

scholarly journals Amyloid Proteins and Peripheral Neuropathy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1553 ◽  
Author(s):  
Mohammed M. H. Asiri ◽  
Sjoukje Engelsman ◽  
Niels Eijkelkamp ◽  
Jo W. M. Höppener
Keyword(s):  
Peripheral Neuropathy ◽  
Potential Role ◽  
Inflammatory Diseases ◽  
Amyloid Proteins ◽  
Chronic Inflammatory Diseases ◽  
Histopathological Feature ◽  
Common Diseases ◽  
Biological Defects

Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature—deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. Here, we will discuss how amyloid proteins contribute to peripheral neuropathy by reviewing the current understanding of pathogenic mechanisms in known inherited and acquired (usually rare) amyloid neuropathies. In addition, we will discuss the potential role of amyloid proteins in peripheral neuropathy in some common diseases, which are not (yet) considered as amyloid neuropathies. We conclude that there are many similarities in the molecular and cell biological defects caused by aggregation of the various amyloid proteins in these different diseases and propose a common pathogenic pathway for “peripheral amyloid neuropathies”.

scholarly journals Oxidation of the Tryptophan 32 Residue of Human Superoxide Dismutase 1 Caused by Its Bicarbonate-dependent Peroxidase Activity Triggers the Non-amyloid Aggregation of the Enzyme

2014 ◽  
Vol 289 (44) ◽  
pp. 30690-30701 ◽  
Author(s):  
Fernando R. Coelho ◽  
Asif Iqbal ◽  
Edlaine Linares ◽  
Daniel F. Silva ◽  
Filipe S. Lima ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Peroxidase Activity ◽  
Oxidation Products ◽  
Superoxide Dismutase 1 ◽  
Amyloid Aggregation ◽  
Post Translational Modifications ◽  
Covalent Dimer ◽  
Als Patients ◽  
Lateral Sclerosis

The role of oxidative post-translational modifications of human superoxide dismutase 1 (hSOD1) in the amyotrophic lateral sclerosis (ALS) pathology is an attractive hypothesis to explore based on several lines of evidence. Among them, the remarkable stability of hSOD1WT and several of its ALS-associated mutants suggests that hSOD1 oxidation may precede its conversion to the unfolded and aggregated forms found in ALS patients. The bicarbonate-dependent peroxidase activity of hSOD1 causes oxidation of its own solvent-exposed Trp32 residue. The resulting products are apparently different from those produced in the absence of bicarbonate and are most likely specific for simian SOD1s, which contain the Trp32 residue. The aims of this work were to examine whether the bicarbonate-dependent peroxidase activity of hSOD1 (hSOD1WT and hSOD1G93A mutant) triggers aggregation of the enzyme and to comprehend the role of the Trp32 residue in the process. The results showed that Trp32 residues of both enzymes are oxidized to a similar extent to hSOD1-derived tryptophanyl radicals. These radicals decayed to hSOD1-N-formylkynurenine and hSOD1-kynurenine or to a hSOD1 covalent dimer cross-linked by a ditryptophan bond, causing hSOD1 unfolding, oligomerization, and non-amyloid aggregation. The latter process was inhibited by tempol, which recombines with the hSOD1-derived tryptophanyl radical, and did not occur in the absence of bicarbonate or with enzymes that lack the Trp32 residue (bovine SOD1 and hSOD1W32F mutant). The results support a role for the oxidation products of the hSOD1-Trp32 residue, particularly the covalent dimer, in triggering the non-amyloid aggregation of hSOD1.

scholarly journals Biological role of bacterial inclusion bodies: a model for amyloid aggregation

FEBS Journal ◽  
2011 ◽  
Vol 278 (14) ◽  
pp. 2419-2427 ◽  
Author(s):  
Elena García-Fruitós ◽  
Raimon Sabate ◽  
Natalia S. de Groot ◽  
Antonio Villaverde ◽  
Salvador Ventura
Keyword(s):  
Inclusion Bodies ◽  
Biological Role ◽  
Amyloid Aggregation

scholarly journals Mitochondria-Microbiota Interaction in Neurodegeneration

2021 ◽  
Vol 13 ◽  
Author(s):  
Peter Kramer
Keyword(s):  
Synaptic Plasticity ◽  
Immune System ◽  
Side Effects ◽  
Neurodegenerative Diseases ◽  
Bile Secretion ◽  
Immune Defense ◽  
Amyloid Aggregation ◽  
Amyloid Proteins ◽  
The Brain

Alzheimer’s and Parkinson’s are the two best-known neurodegenerative diseases. Each is associated with the excessive aggregation in the brain and elsewhere of its own characteristic amyloid proteins. Yet the two afflictions have much in common and often the same amyloids play a role in both. These amyloids need not be toxic and can help regulate bile secretion, synaptic plasticity, and immune defense. Moreover, when they do form toxic aggregates, amyloids typically harm not just patients but their pathogens too. A major port of entry for pathogens is the gut. Keeping the gut’s microbe community (microbiota) healthy and under control requires that our cells’ main energy producers (mitochondria) support the gut-blood barrier and immune system. As we age, these mitochondria eventually succumb to the corrosive byproducts they themselves release, our defenses break down, pathogens or their toxins break through, and the side effects of inflammation and amyloid aggregation become problematic. Although it gets most of the attention, local amyloid aggregation in the brain merely points to a bigger problem: the systemic breakdown of the entire human superorganism, exemplified by an interaction turning bad between mitochondria and microbiota.

scholarly journals Structural basis of the interplay between α-synuclein and Tau in regulating pathological amyloid aggregation

2020 ◽  
Vol 295 (21) ◽  
pp. 7470-7480 ◽  
Author(s):  
Jinxia Lu ◽  
Shengnan Zhang ◽  
Xiaojuan Ma ◽  
Chunyu Jia ◽  
Zhenying Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Direct Interaction ◽  
Structural Basis ◽  
Amyloid Aggregation ◽  
C Terminus ◽  
Amyloid Fibrillation

Amyloid aggregation of pathological proteins is closely associated with a variety of neurodegenerative diseases, and α-synuclein (α-syn) deposition and Tau tangles are considered hallmarks of Parkinson's disease and Alzheimer's disease, respectively. Intriguingly, α-syn and Tau have been found to co-deposit in the brains of individuals with dementia and parkinsonism, suggesting a potential role of cross-talk between these two proteins in neurodegenerative pathologies. Here we show that monomeric α-syn and the two variants of Tau, Tau23 and K19, synergistically promote amyloid fibrillation, leading to their co-aggregation in vitro. NMR spectroscopy experiments revealed that α-syn uses its highly negatively charged C terminus to directly interact with Tau23 and K19. Deletion of the C terminus effectively abolished its binding to Tau23 and K19 as well as its synergistic effect on promoting their fibrillation. Moreover, an S129D substitution of α-syn, mimicking C-terminal phosphorylation of Ser129 in α-syn, which is commonly observed in the brains of Parkinson's disease patients with elevated α-syn phosphorylation levels, significantly enhanced the activity of α-syn in facilitating Tau23 and K19 aggregation. These results reveal the molecular basis underlying the direct interaction between α-syn and Tau. We proposed that this interplay might contribute to pathological aggregation of α-syn and Tau in neurodegenerative diseases.

The role of metals in amyloid aggregation—Experiments and ab initio simulations

2008 ◽  
Vol 108 (11) ◽  
pp. 1992-2015 ◽  
Author(s):  
V. Minicozzi ◽  
S. Morante ◽  
G. C. Rossi ◽  
F. Stellato ◽  
N. Christian ◽  
...  
Keyword(s):  
Ab Initio ◽  
Amyloid Aggregation ◽  
Ab Initio Simulations

scholarly journals sw ApoMb Amyloid Aggregation under Nondenaturing Conditions: The Role of Native Structure Stability

2017 ◽  
Vol 113 (5) ◽  
pp. 991-1001 ◽  
Author(s):  
Natalya S. Katina ◽  
Vitalii A. Balobanov ◽  
Nelly B. Ilyina ◽  
Victor D. Vasiliev ◽  
Victor V. Marchenkov ◽  
...  
Keyword(s):  
Structure Stability ◽  
Amyloid Aggregation ◽  
Native Structure
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