Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

Sirangelo, Ivana; Borriello, Margherita; Vilasi, Silvia

doi:10.3390/ijms21134636

Cited by 23 publications

(15 citation statements)

References 71 publications

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“…The protective effect of polyphenols has also been indicated in breaking up the pathological aggregates formed by Aβ and tau [ 153 ]. Hydroxytyrosol is able to inhibit insulin amyloid formation and completely reverse the toxicity induced by amyloid insulin aggregates in the cell [ 154 ]. Therefore, polyphenols provide a promising approach for targeting neurodegenerative diseases.…”

Section: Other Factors Regulating Functional Protein Aggregationmentioning

confidence: 99%

Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins

Sheng

Olrichs

Gadella

et al. 2020

IJMS

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The idea that amyloid fibrils and other types of protein aggregates are toxic for cells has been challenged by the discovery of a variety of functional aggregates. However, an identification of crucial differences between pathological and functional aggregation remains to be explored. Functional protein aggregation is often reversible by nature in order to respond properly to changing physiological conditions of the cell. In addition, increasing evidence indicates that fast fibril growth is a feature of functional amyloids, providing protection against the long-term existence of potentially toxic oligomeric intermediates. It is becoming clear that functional protein aggregation is a complexly organized process that can be mediated by a multitude of biomolecular factors. In this overview, we discuss the roles of diverse biomolecules, such as lipids/membranes, glycosaminoglycans, nucleic acids and metal ions, in regulating functional protein aggregation. Our studies on the protein GAPR-1 revealed that several of these factors influence the amyloidogenic properties of this protein. These observations suggest that GAPR-1, as well as the cysteine-rich secretory proteins, antigen 5 and pathogenesis-related proteins group 1 (CAP) superfamily of proteins that it belongs to, require the assembly into an amyloid state to exert several of their functions. A better understanding of functional aggregate formation may also help in the prevention and treatment of amyloid-related diseases.

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Section: Other Factors Regulating Functional Protein Aggregationmentioning

confidence: 99%

Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins

Sheng

Olrichs

Gadella

et al. 2020

IJMS

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“…Secondly, we triggered the insulin amyloid formation (at 50 °C under stirring) and studied how the fibrillogenesis process was influenced by the presence of GroEL/GroES. In fact, although insulin amyloid aggregation has been well characterised under acidic conditions also at neutral pH, the protein can aggregate, forming amyloid structures [ 40 , 41 , 42 ]. Both classes of experiments were carried out at pH 7.4 and in a buffer, called refolding buffer (100 mM KCl, 5 mM MgCl 2 and 0.1 mM ATP in 50 mM Tris, pH 7.5) containing all the ingredients necessary for the functioning of the GroEL/GroES molecular machine solution [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

The Possible Role of the Type I Chaperonins in Human Insulin Self-Association

Pizzo

Mangione

Librizzi

et al. 2022

Life

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Insulin is a hormone that attends to energy metabolism by regulating glucose levels in the bloodstream. It is synthesised within pancreas beta-cells where, before being released into the serum, it is stored in granules as hexamers coordinated by Zn2+ and further packaged in microcrystalline structures. The group I chaperonin cpn60, known for its assembly-assisting function, is present, together with its cochaperonin cpn10, at each step of the insulin secretory pathway. However, the exact function of the heat shock protein in insulin biosynthesis and processing is still far from being understood. Here we explore the possibility that the molecular machine cpn60/cpn10 could have a role in insulin hexameric assembly and its further crystallization. Moreover, we also evaluate their potential protective effect in pathological insulin aggregation. The experiments performed with the cpn60 bacterial homologue, GroEL, in complex with its cochaperonin GroES, by using spectroscopic methods, microscopy and hydrodynamic techniques, reveal that the chaperonins in vitro favour insulin hexameric organisation and inhibit its aberrant aggregation. These results provide new details in the field of insulin assembly and its related disorders.

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“…In this respect, much attention has been paid to natural compounds, such as polyphenols, well known for their antioxidants and anti-inflammatory properties, able to prevent/protect by neurodegenerative diseases [ 190 , 191 , 192 , 193 , 194 , 195 , 196 ]. Several studies have suggested that natural phenolic compounds can interfere both with protein glycation and with the amyloid aggregation process of several model proteins [ 194 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 ]. In this context, polyphenols could represent an efficient additional therapy capable of acting on several mechanisms common to the pathologies of diabetes and amyloidosis simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Role of Protein Glycation in the Amyloid Aggregation Process

Sirangelo

2021

IJMS

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Protein function and flexibility is directly related to the native distribution of its structural elements and any alteration in protein architecture leads to several abnormalities and accumulation of misfolded proteins. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidosis characterized by the accumulation of amyloid aggregates both in the extracellular space of tissues and as intracellular deposits. Post-translational modifications are known to have an active role in the in vivo amyloid aggregation as able to affect protein structure and dynamics. Among them, a key role seems to be played by non-enzymatic glycation, the most unwanted irreversible modification of the protein structure, which strongly affects long-living proteins throughout the body. This study provided an overview of the molecular effects induced by glycation on the amyloid aggregation process of several protein models associated with misfolding diseases. In particular, we analyzed the role of glycation on protein folding, kinetics of amyloid formation, and amyloid cytotoxicity in order to shed light on the role of this post-translational modification in the in vivo amyloid aggregation process.

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Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

Cited by 23 publications

References 71 publications

Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins

Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins

The Possible Role of the Type I Chaperonins in Human Insulin Self-Association

Understanding the Role of Protein Glycation in the Amyloid Aggregation Process

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