Inhibiting Islet Amyloid Polypeptide Fibril Formation by the Red Wine Compound Resveratrol

Mishra, Rajesh; Sellin, Daniel; Radovan, Diana; Gohlke, Andrea; Winter, Roland

doi:10.1002/cbic.200800762

Cited by 123 publications

(136 citation statements)

References 32 publications

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“…Therefore, considerable efforts are being devoted to the development of new anti-aggregating agents, particularly in relation to amyloid-related peptides and proteins, under both in vitro and in vivo conditions [15][16][17][18][19][20][21][22][23]. In this regard, numerous reports have demonstrated the effectiveness of some of the naturally occurring small molecules, and specially certain natural polyphenols, on prevention of protein aggregation and their associated cytotoxicity [24][25][26][27][28][29][30][31]. Recently, we too, have reported on inhibition of fibrillation as well as destabilization of preformed fibrils of A␤ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), using a range of small molecules, including polyphenols [32].…”

Section: Q2mentioning

confidence: 99%

Inhibition of amyloid fibrillation and cytotoxicity of lysozyme fibrillation products by polyphenols

Shariatizi

Meratan

Ghasemi

et al. 2015

International Journal of Biological Macromolecules

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Section: Q2mentioning

confidence: 99%

Inhibition of amyloid fibrillation and cytotoxicity of lysozyme fibrillation products by polyphenols

Shariatizi

Meratan

Ghasemi

et al. 2015

International Journal of Biological Macromolecules

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“…The secondary structures are primarily stabilized by hydrogen bonding between the amino-and carbonyl groups of the main chain(s) (···) [169]. In β-sheets, the amino acid side groups (R) are directed orthogonal to the sheet plane and systematically decorate both surfaces [165] since CR and some of the small organic molecules related to CR and ThT structures have been shown to inhibit fibril formation [28][29][30][31]. This review will give an overview of the classic as well as new molecular probes for amyloid fibril detection and a deeper insight into the recent understanding of their binding modes.…”

Section: Introductionmentioning

confidence: 99%

Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils—current status

2009

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Because understanding amyloid fibrillation in molecular detail is essential for development of strategies to control amyloid formation and overcome neurodegenerative disorders, increased understanding of present molecular probes as well as development of new probes are of utmost importance. To date, the binding modes of these molecular probes to amyloid fibrils are by no means adequately described or understood, and the large number of studies on Thioflavin T (ThT) and Congo Red (CR) binding have resulted in models that are incomplete and conflicting. Different types of binding sites are likely to be present in amyloid fibrils with differences in binding modes. ThT may bind in channels running parallel to the long axis of the fibril. In the channels, ThT may bind in either a monomeric or dimeric form of which the molecular conformation is likely to be planar. CR may bind in grooves formed along the β-sheets as a planar molecule in either a monomeric or supramolecular form.

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“…However, although many of these compounds have been tested in mice, not all of them would be suitable for clinical use. Alternative inhibitors which could be administered to humans have included some aromatic compounds including resevatrol (a component of red wine) (Porat et al 2004, Evers et al 2009, Mishra et al 2009) and some polyphenols including (−)-Epigallocatechin 3-Gallate (EGCG) (a natural component of green tea); inhibition of fibrillogenesis was accompanied by disaggregation of fibrils and formation of non-toxic oligomers (Meng et al 2010, Engel et al 2012. Other inhibitors effective in vitro are tetracycline, congo red, ruthenium red, and organic designed 'foldamers' (Aitken et al 2003, Kumar & Miranker 2013, Zhu et al 2017.…”

Section: Inhibitors Of Iapp Fibrillogenesis: a Suitable Treatment In mentioning

confidence: 99%

The β-cell assassin: IAPP cytotoxicity

Raleigh

Zhang

Hastoy

et al. 2017

Journal of Molecular Endocrinology

103

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Islet amyloid polypeptide (IAPP) forms cytotoxic oligomers and amyloid fibrils in islets in type 2 diabetes (T2DM). The causal factors for amyloid formation are largely unknown. Mechanisms of molecular folding and assembly of human IAPP (hIAPP) into β-sheets, oligomers and fibrils have been assessed by detailed biophysical studies of hIAPP and non-fibrillogenic, rodent IAPP (rIAPP); cytotoxicity is associated with the early phases (oligomers/multimers) of fibrillogenesis. Interaction with synthetic membranes promotes β-sheet assembly possibly via a transient α-helical molecular conformation. Cellular hIAPP cytotoxicity can be activated from intracellular or extracellular sites. In transgenic rodents overexpressing hIAPP, intracellular pro-apoptotic signals can be generated at different points in β-cell protein synthesis. Increased cellular trafficking of proIAPP, failure of the unfolded protein response (UPR) or excess trafficking of misfolded peptide via the degradation pathways can induce apoptosis; these data indicate that defects in intracellular handling of hIAPP can induce cytotoxicity. However, there is no evidence for IAPP overexpression in T2DM. Extracellular amyloidosis is directly related to the degree of β-cell apoptosis in islets in T2DM. IAPP fragments, fibrils and multimers interact with membranes causing disruption in vivo and in vitro. These findings support a role for extracellular IAPP in β-sheet conformation in cytotoxicity. Inhibitors of fibrillogenesis are useful tools to determine the aberrant mechanisms that result in hIAPP molecular refolding and islet amyloidosis. However, currently, their role as therapeutic agents remains uncertain.

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Inhibiting Islet Amyloid Polypeptide Fibril Formation by the Red Wine Compound Resveratrol

Cited by 123 publications

References 32 publications

Inhibition of amyloid fibrillation and cytotoxicity of lysozyme fibrillation products by polyphenols

Inhibition of amyloid fibrillation and cytotoxicity of lysozyme fibrillation products by polyphenols

Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils—current status

The β-cell assassin: IAPP cytotoxicity

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