Molecular mechanisms of amyloid aggregation in human proteinopathies

2020 ◽  
pp. 153-179
Author(s):  
Bertrand Morel ◽  
Francisco Conejero-Lara
Keyword(s):  
Molecular Mechanisms ◽  
Amyloid Aggregation

Ferrocene-modified peptides as inhibitors against insulin amyloid aggregation based on molecular simulation

2020 ◽  
Vol 8 (15) ◽  
pp. 3076-3086
Author(s):  
Pin Yao ◽  
Jiaxing Zhang ◽  
Shengping You ◽  
Wei Qi ◽  
Rongxin Su ◽  
...  
Keyword(s):  
Molecular Simulation ◽  
Molecular Mechanisms ◽  
Amyloid Aggregation ◽  
Modified Peptides

Developed Fc-peptides (Fc-FF and Fc-FY) as effective inhibitors of insulin amyloid aggregation and revealed molecular mechanisms of inhibition.

scholarly journals Catechins as Tools to Understand the Molecular Basis of Neurodegeneration

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3571
Author(s):  
Karla Martinez Pomier ◽  
Rashik Ahmed ◽  
Giuseppe Melacini
Keyword(s):  
Phenolic Compounds ◽  
Neurodegenerative Disorders ◽  
Molecular Basis ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Amyloid Aggregation ◽  
Amyloid Aggregates ◽  
Parkinson’S Diseases ◽  
Pharmacokinetic Properties ◽  
Self Association

Protein misfolding as well as the subsequent self-association and deposition of amyloid aggregates is implicated in the progression of several neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Modulators of amyloidogenic aggregation serve as essential tools to dissect the underlying molecular mechanisms and may offer insight on potential therapeutic solutions. These modulators include green tea catechins, which are potent inhibitors of amyloid aggregation. Although catechins often exhibit poor pharmacokinetic properties and bioavailability, they are still essential tools for identifying the drivers of amyloid aggregation and for developing other aggregation modulators through structural mimicry. As an illustration of such strategies, here we review how catechins have been used to map the toxic surfaces of oligomeric amyloid-like species and develop catechin-based phenolic compounds with enhanced anti-amyloid activity.

scholarly journals Neuroprotective Effect of Fagopyrum dibotrys Extract against Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Chen Liang ◽  
Jian-Ping Yuan ◽  
Tao Ding ◽  
Lv Yan ◽  
Lu Ling ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Amyloid Aggregation ◽  
Traditional Herbal Medicine ◽  
Reactive Microglia ◽  
Polyphenolic Antioxidants ◽  
Neuroprotective Actions ◽  
The Brain

Accumulated evidence suggests that polyphenolic antioxidants present in herbs play important roles in prevention of AD; the molecular mechanisms behind neuroprotective actions rely on the phenols through different effects on the amyloid-aggregation pathway. Fagopyrum dibotrys is a traditional herbal medicine which contains high quantity phenols. In present study, we investigate the beneficial pharmacological actions of Fagopyrum dibotrys extract in the APP/PS1 transgenic mouse mode; meanwhile, effects of the FDE on the fibrillation and cytotoxicity of Aβ peptide were evaluated in vitro. After 9-month treatment, FDE exhibited multifunctional properties on Aβ-related pathologies, which cleaned Aβ deposits in the brain and decreased Aβ burden in the plasma, inhibited microhaemorrhage, and reduced reactive microglia in APP/PS1 transgenic mice and also promoted Aβ fibrils disaggregation and inhibited neurotoxicity induced by Aβ in SH-SY5Y cells. These results highlighted that FDE is an AD type pathology modulator with therapeutic potential against AD.

scholarly journals Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

2020 ◽  
Vol 21 (13) ◽  
pp. 4636
Author(s):  
Ivana Sirangelo ◽  
Margherita Borriello ◽  
Silvia Vilasi ◽  
Clara Iannuzzi
Keyword(s):  
Olive Oil ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cell ◽  
Biological Properties ◽  
Protein Oligomerization ◽  
Amyloid Aggregation ◽  
Beneficial Effects ◽  
Phenolic Components ◽  
Biophysical Approach

Hydroxytyrosol (HT), one of the main phenolic components of olive oil, has attracted considerable interest for its biological properties, including a remarkable antioxidant and anti-inflammatory power and, recently, for its ability to interfere with the amyloid aggregation underlying several human diseases. We report here a broad biophysical approach and cell biology techniques that allowed us to characterize the molecular mechanisms by which HT affects insulin amyloid aggregation and the related cytotoxicity. Our data show that HT is able to fully inhibit insulin amyloid aggregation and this property seems to be ascribed to the stabilization of the insulin monomeric state. Moreover, HT completely reverses the toxic effect produced by amyloid insulin aggregates in neuroblastoma cell lines by fully inhibiting the production of toxic amyloid species. These findings suggest that the beneficial effects of olive oil polyphenols, including HT, may arise from multifunctional activities and suggest possible a application of this natural compound in the prevention or treatment of amyloid-associated diseases.

scholarly journals Contrasting effects of nanoparticle–protein attraction on amyloid aggregation

RSC Advances ◽  
2015 ◽  
Vol 5 (127) ◽  
pp. 105489-105498 ◽  
Author(s):  
Slaven Radic ◽  
Thomas P. Davis ◽  
Pu Chun Ke ◽  
Feng Ding
Keyword(s):  
Molecular Mechanisms ◽  
Amyloid Aggregation

Nanoparticles (NPs) have been experimentally found to either promote or inhibit amyloid aggregation of proteins, but the molecular mechanisms for such complex behaviors remain unknown.

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

Dissection of the molecular mechanisms of protein targeting to the peroxisome using immunofluorescence and immunocryoelectron microscopies

1990 ◽  
Vol 48 (3) ◽  
pp. 44-45
Author(s):  
G-A. Keller ◽  
S. J. Gould ◽  
S. Subramani ◽  
S. Krisans
Keyword(s):  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Protein Targeting ◽  
Firefly Luciferase ◽  
Peroxisomal Enzyme ◽  
Transfected Cells ◽  
Peroxisomal Targeting ◽  
Targeting Signal ◽  
Series Of Experiments ◽  
Peroxisomal Targeting Signal

Subcellular compartments within eukaryotic cells must each be supplied with unique sets of proteins that must be directed to, and translocated across one or more membranes of the target organelles. This transport is mediated by cis- acting targeting signals present within the imported proteins. The following is a chronological account of a series of experiments designed and carried out in an effort to understand how proteins are targeted to the peroxisomal compartment.-We demonstrated by immunocryoelectron microscopy that the enzyme luciferase is a peroxisomal enzyme in the firefly lantern. -We expressed the cDNA encoding firefly luciferase in mammalian cells and demonstrated by immunofluorescence that the enzyme was transported into the peroxisomes of the transfected cells. -Using deletions, linker insertions, and gene fusion to identify regions of luciferase involved in its transport to the peroxisomes, we demonstrated that luciferase contains a peroxisomal targeting signal (PTS) within its COOH-terminal twelve amino acid.

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