Challenges in studying the structures of metal-amyloid oligomers related to type 2 diabetes, Parkinson's disease, and Alzheimer's disease

Wineman-Fisher, Vered; Bloch, Daniel Nir; Miller, Yifat

doi:10.1016/j.ccr.2016.04.010

Cited by 21 publications

(18 citation statements)

References 92 publications

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“…In addition, Aβ His residues have been reported to bind to discrete metal complexes such as heme,34 a Ru complexes,22a,23a,39 and Co complexes 10b,24. In addition to His binding, residues Asp 1 , Tyr 10 , and Glu 11 play a role in the coordination of Aβ to Cu( ii ) and Zn( ii ) 40…”

Section: Resultsmentioning

confidence: 99%

A catalytic antioxidant for limiting amyloid-beta peptide aggregation and reactive oxygen species generation

et al. 2019

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Section: Resultsmentioning

confidence: 99%

A catalytic antioxidant for limiting amyloid-beta peptide aggregation and reactive oxygen species generation

et al. 2019

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“…Detailed analyses of Cu(II) and Zn(II) binding to Aβ have shown different effects on peptide aggregation depending on the experimental conditions [38,118,129,130]. The different aggregation pathways might arise from the coordination of multiple Aβ peptides to the same metal ion, which likely is an important factor in Aβ aggregation [130,131]. Although our NMR data indicate that the histidine residues are the main binding ligands to Hg(II) (Figure 4), other N-terminal residues such as Asp1, Glu3, Asp7, Tyr10, and Glu11 are also possible binding partners.…”

Section: The In Vitro Analyses Of the Hg(ii)•aβ Complexes And Their Amentioning

confidence: 99%

“…When a single Aβ peptide coordinates a single metal ion, the peptide appears to adopt a structure unsuitable for fibril formation [118]. Coordinating one metal ion to two or more Aβ peptides usually promotes aggregation, but not necessarily fibrillization [130,131]. In particular, supra-stoichiometric amounts of metal ions often induce rapid formation of amorphous aggregates instead of fibrils [38,132].…”

Section: The In Vitro Analyses Of the Hg(ii)•aβ Complexes And Their Amentioning

confidence: 99%

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

et al. 2019

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Brains and blood of Alzheimer’s disease (AD) patients have shown elevated mercury concentrations, but potential involvement of mercury exposure in AD pathogenesis has not been studied at the molecular level. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. Aβ peptide fibrillization is known to be modulated by metal ions such as Cu(II) and Zn(II). Here, we study in vitro the interactions between Aβ peptides and Hg(II) ions by multiple biophysical techniques. Fluorescence spectroscopy and atomic force microscopy (AFM) show that Hg(II) ions have a concentration-dependent inhibiting effect on Aβ fibrillization: at a 1:1 Aβ·Hg(II) ratio only non-fibrillar Aβ aggregates are formed. NMR spectroscopy shows that Hg(II) ions interact with the N-terminal region of Aβ(1–40) with a micromolar affinity, likely via a binding mode similar to that for Cu(II) and Zn(II) ions, i.e., mainly via the histidine residues His6, His13, and His14. Thus, together with Cu(II), Fe(II), Mn(II), Pb(IV), and Zn(II) ions, Hg(II) belongs to a family of metal ions that display residue-specific binding interactions with Aβ peptides and modulate their aggregation processes.

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“…IAPP has been identified due to its ability to aggregate in the amyloid deposits of pancreatic islets, which are seen primarily in association with type 2 diabetes in humans and diabetes in several other mammalian species, especially monkeys and cats [ 23 ]. At present, it is increasingly accepted that there are close correlations between these two diseases by overlapping their pathology, sharing common complications including impaired carbohydrate metabolism, insulin resistance, oxidative stress, inflammatory response, mitochondrial dysfunction, and amyloidosis ( Figure 2 ) [ 24 ].…”

Section: Amyloid Formation As a Common Pathological Feature In Botmentioning

confidence: 99%

Link between Diabetes and Alzheimer’s Disease Due to the Shared Amyloid Aggregation and Deposition Involving Both Neurodegenerative Changes and Neurovascular Damages

Stanciu

Bild

Ababei

et al. 2020

JCM

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Diabetes and Alzheimer’s disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms “diabetes type 3” or “brain diabetes” have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-β aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer’s disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development.

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Challenges in studying the structures of metal-amyloid oligomers related to type 2 diabetes, Parkinson's disease, and Alzheimer's disease

Cited by 21 publications

References 92 publications

A catalytic antioxidant for limiting amyloid-beta peptide aggregation and reactive oxygen species generation

A catalytic antioxidant for limiting amyloid-beta peptide aggregation and reactive oxygen species generation

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

Link between Diabetes and Alzheimer’s Disease Due to the Shared Amyloid Aggregation and Deposition Involving Both Neurodegenerative Changes and Neurovascular Damages

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