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 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.

scholarly journals Thermodynamics of Homopeptide Aggregation

2020 ◽  
Author(s):  
Tam T. M. Phan ◽  
Jeremy D. Schmit
Keyword(s):  
Neurodegenerative Diseases ◽  
Disease Progression ◽  
Prion Diseases ◽  
Steric Repulsion ◽  
Polymer Micelles ◽  
Amyloid Aggregates ◽  
Exon 1 ◽  
Flanking Sequences ◽  
Precise Role

ABSTRACTAmyloid aggregates are found in many neurodegenerative diseases including Huntington’s, Alzheimer’s, and prion diseases. The precise role of the aggregates in disease progression has been difficult to elucidate due to the diversity of aggregated states they can adopt. Here we study the formation of fibrils and oligomers by exon 1 of huntingtin protein. We show that the oligomer states are consistent with polymer micelles that are limited in size by the stretching entropy of the polyglutamine region. The model shows how the sequences flanking the amyloid core modulate aggregation behavior. The N17 region promotes aggregation through weakly attractive interactions, while the C38 tail opposes aggregation via steric repulsion. We also show that the energetics of cross-β stacking by polyglutamine would produce fibrils with many alignment defects, but minor perturbations from the flanking sequences are sufficient to reduce the defects to the level observed in experiment. We conclude with a discussion of the implications of this model for other amyloid forming molecules.

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

scholarly journals The Role of Vesicle Trafficking Defects in the Pathogenesis of Prion and Prion-Like Disorders

2020 ◽  
Vol 21 (19) ◽  
pp. 7016
Author(s):  
Pearl Cherry ◽  
Sabine Gilch
Keyword(s):  
Neurodegenerative Diseases ◽  
Prion Diseases ◽  
Primary Component ◽  
Vesicular Trafficking ◽  
Polyglutamine Diseases ◽  
Amyloid Aggregates ◽  
The Common ◽  
Trafficking Defects ◽  
Insight Into

Prion diseases are fatal and transmissible neurodegenerative diseases in which the cellular form of the prion protein ‘PrPc’, misfolds into an infectious and aggregation prone isoform termed PrPSc, which is the primary component of prions. Many neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and polyglutamine diseases, such as Huntington’s disease, are considered prion-like disorders because of the common characteristics in the propagation and spreading of misfolded proteins that they share with the prion diseases. Unlike prion diseases, these are non-infectious outside experimental settings. Many vesicular trafficking impairments, which are observed in prion and prion-like disorders, favor the accumulation of the pathogenic amyloid aggregates. In addition, many of the vesicular trafficking impairments that arise in these diseases, turn out to be further aggravating factors. This review offers an insight into the currently known vesicular trafficking defects in these neurodegenerative diseases and their implications on disease progression. These findings suggest that these impaired trafficking pathways may represent similar therapeutic targets in these classes of neurodegenerative disorders.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

External Factors of Big Business Transformation in Russia

2005 ◽  
pp. 72-89 ◽  
Author(s):  
Ya. Pappe ◽  
Ya. Galukhina
Keyword(s):  
Financial Market ◽  
Capital Market ◽  
Business Groups ◽  
External Factors ◽  
Big Business ◽  
Business Transformation ◽  
Global Standards ◽  
The World ◽  
Principal Subject

The paper is devoted to the role of the global financial market in the development of Russian big business. It proves that terms and standards posed by this market as well as opportunities it offers determine major changes in Russian big business in the last three years. The article examines why Russian companies go abroad to attract capital and provides data, which indicate the scope of this phenomenon. It stresses the effects of Russian big business’s interaction with the world capital market, including the modification of the principal subject of Russian big business from integrated business groups to companies and the changes in companies’ behavior: they gradually move away from the so-called Russian specifics and adopt global standards.

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