scholarly journals Seeding of proteins into amyloid structures by metabolite assemblies may clarify certain unexplained epidemiological associations

Open Biology ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 170229 ◽  
Author(s):  
Dorin Sade ◽  
Shira Shaham-Niv ◽  
Zohar A. Arnon ◽  
Omid Tavassoly ◽  
Ehud Gazit
Keyword(s):  
Protein Aggregation ◽  
Quinolinic Acid ◽  
Inborn Error ◽  
Amyloid Formation ◽  
Loss Of Function ◽  
New Paradigm ◽  
Mechanistic Insight ◽  
Degenerative Disorders ◽  
Metabolite Accumulation ◽  
Insight Into

The accumulation of various metabolites appears to be associated with diverse human diseases. However, the aetiological link between metabolic alteration and the observed diseases is still elusive. This includes the correlation between the abnormally high levels of homocysteine and quinolinic acid in Alzheimer's disease, as well as the accumulation of oncometabolites in malignant processes. Here, we suggest and discuss a possible mechanistic insight into metabolite accumulation in conditions such as neurodegenerative diseases and cancer. Our hypothesis is based on the demonstrated ability of metabolites to form amyloid-like structures in inborn error of metabolism disorders and the potential of such metabolite amyloids to promote protein aggregation. This notion can provide a new paradigm for neurodegeneration and cancer, as both conditions were linked to loss of function due to protein aggregation. Similar to the well-established observation of amyloid formation in many degenerative disorders, the formation of amyloids by tumour-suppressor proteins, including p53, was demonstrated in malignant states. Moreover, this new paradigm could fill the gap in understanding the high occurrence of specific types of cancer among genetic error of metabolism patients. This hypothesis offers a fresh view on the aetiology of some of the most abundant human maladies and may redirect the efforts towards new therapeutic developments.

Mechanistic insight into the early stages of amyloid formation using an anuran peptide

2019 ◽  
Vol 111 (5) ◽  
Author(s):  
Sourav Ray ◽  
Stephanie Holden ◽  
Lisandra L. Martin ◽  
Ajay Singh Panwar
Keyword(s):  
Amyloid Formation ◽  
Early Stages ◽  
Mechanistic Insight ◽  
Insight Into

scholarly journals Novel Mechanistic Insight into the Molecular Basis of Amyloid Polymorphism and Secondary Nucleation during Amyloid Formation

2013 ◽  
Vol 425 (10) ◽  
pp. 1765-1781 ◽  
Author(s):  
Jae Sun Jeong ◽  
Annalisa Ansaloni ◽  
Raffaele Mezzenga ◽  
Hilal A. Lashuel ◽  
Giovanni Dietler
Keyword(s):  
Molecular Basis ◽  
Amyloid Formation ◽  
Secondary Nucleation ◽  
Mechanistic Insight ◽  
Insight Into

scholarly journals Protein Aggregation as a Bacterial Strategy to Survive Antibiotic Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Celien Bollen ◽  
Liselot Dewachter ◽  
Jan Michiels
Keyword(s):  
Oxidative Stress ◽  
Protein Aggregation ◽  
Antibiotic Treatment ◽  
Bacterial Survival ◽  
Loss Of Function ◽  
Vbnc State ◽  
Persister Cells ◽  
Dormant Cells ◽  
Heat Shocks ◽  
Insight Into

While protein aggregation is predominantly associated with loss of function and toxicity, it is also known to increase survival of bacteria under stressful conditions. Indeed, protein aggregation not only helps bacteria to cope with proteotoxic stresses like heat shocks or oxidative stress, but a growing number of studies suggest that it also improves survival during antibiotic treatment by inducing dormancy. A well-known example of dormant cells are persisters, which are transiently refractory to the action of antibiotics. These persister cells can switch back to the susceptible state and resume growth in the absence of antibiotics, and are therefore considered an important cause of recurrence of infections. Mounting evidence now suggests that this antibiotic-tolerant persister state is tightly linked to—or perhaps even driven by—protein aggregation. Moreover, another dormant bacterial phenotype, the viable but non-culturable (VBNC) state, was also shown to be associated with aggregation. These results indicate that persisters and VBNC cells may constitute different stages of the same dormancy program induced by progressive protein aggregation. In this mini review, we discuss the relation between aggregation and bacterial dormancy, focusing on both persisters and VBNC cells. Understanding the link between protein aggregation and dormancy will not only provide insight into the fundamentals of bacterial survival, but could prove highly valuable in our future battle to fight them.

The physical chemistry of the amyloid phenomenon: thermodynamics and kinetics of filamentous protein aggregation

2014 ◽  
Vol 56 ◽  
pp. 11-39 ◽  
Author(s):  
Alexander K. Buell ◽  
Christopher M. Dobson ◽  
Tuomas P.J. Knowles
Keyword(s):  
Protein Aggregation ◽  
Molecular Chaperones ◽  
Amyloid Fibrils ◽  
Theoretical Modelling ◽  
Amyloid Formation ◽  
Recent Developments ◽  
The Individual ◽  
Kinetics Of ◽  
Soluble State ◽  
Insight Into

In this chapter, we present an overview of the kinetics and thermodynamics of protein aggregation into amyloid fibrils. The perspective we adopt is largely experimental, but we also discuss recent developments in data analysis and we show that only a combination of well-designed experiments with appropriate theoretical modelling is able to provide detailed mechanistic insight into the complex pathways of amyloid formation. In the first part of the chapter, we describe measurements of the thermodynamic stability of the amyloid state with respect to the soluble state of proteins, as well as the magnitude and origin of this stability. In the second part, we discuss in detail the kinetics of the individual molecular steps in the overall mechanism of the conversion of soluble protein into amyloid fibrils. Finally, we highlight the effects of external factors, such as salt type and concentration, chemical denaturants and molecular chaperones on the kinetics of aggregation.

scholarly journals Mechanistic insight into B(C6F5)3 catalyzed imine reduction with PhSiH3 under stoichiometric water conditions

RSC Advances ◽  
2021 ◽  
Vol 11 (34) ◽  
pp. 20961-20969
Author(s):  
Yunqing He ◽  
Wanli Nie ◽  
Ying Xue ◽  
Qishan Hu
Keyword(s):  
Mechanistic Insight ◽  
Excess Water ◽  
Water Conditions ◽  
Imine Reduction ◽  
Water Amount ◽  
Insight Into

Hydrosilylation or amination products? It depends on water amount and nucleophiles like excess water or produced/added amines.

scholarly journals Mechanistic insight into the fluorescence activity of forensic fingerprinting reagents

2021 ◽  
Vol 154 (12) ◽  
pp. 124313
Author(s):  
L. M. Hunnisett ◽  
P. F. Kelly ◽  
S. Bleay ◽  
F. Plasser ◽  
R. King ◽  
...  
Keyword(s):  
Mechanistic Insight ◽  
Insight Into
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