Change and stabilization of the amyloid-β(1–40) secondary structure by fluorocompounds

Vieira, Euridice P.; Hermel, H.; Möhwald, Helmuth

doi:10.1016/s1570-9639(02)00461-2

Cited by 54 publications

(48 citation statements)

References 40 publications

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“…Conformational studies using circular dichroism (CD) show that in aqueous solution A β42 contains elements of α-helical and β-sheet structure [84,85] while Aβ40 exists primarily as a random coil [27]. Both peptides display a high helical content in fluorinated alcohols [86][87][88][89], an observation consistent with CD and NMR studies of short peptide fragments under a variety of non-aqueous conditions. NMR studies of the full length peptides in aqueous solution have been hampered by their aggregation-prone nature since resonance line widths rapidly broaden and become uninterpretable.…”

Section: Addl Preparation and Isolationsupporting

confidence: 57%

The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease

Catalano

Dodson²,

Henze³

et al. 2006

CTMC

102

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The amyloid-beta (Abeta) cascade hypothesis of Alzheimer's disease (AD) has dominated research and subsequent therapeutic drug development for over two decades. Central to this hypothesis is the observation that Abeta is elevated in AD patients and that the disease is ultimately characterized by the central deposition of insoluble senile plaques. More recent evidence, however, suggests that the presence or absence of plaque is insufficient to fully account for the deleterious role of elevated Abeta in AD. Such studies support the basis for an alternate interpretation of the Abeta cascade hypothesis. Namely, that soluble oligomers of Abeta (i.e., ADDLs) accumulate and cause functional deficits prior to overt neuronal cell death or plaque deposition. Accordingly, the following review focuses on research describing the preparation and functional activity of ADDLs in vitro and in vivo. These studies provide the basis for an alternate, ADDL-based, view of the Abeta cascade hypothesis and accounts for the disconnect between plaque burden and cognitive deficits. Possible therapeutic approaches aimed at lowering ADDLs in AD patients are also considered.

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Section: Addl Preparation and Isolationsupporting

confidence: 57%

The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease

Catalano

Dodson²,

Henze³

et al. 2006

CTMC

102

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“…Adsorption of Ab solutions on poly(tetrafluoroethylene) surfaces have shown that the fluorinated surface strongly promotes a-helix formation; [33] a similar effect was found by studying solutions of Ab in fluorinated solvents. [34] Moreover, organofluorine compounds are effective inhibitors of Ab40 fibrillogenesis [35] and analogues of diflunisal were found to inhibit transthyretin oligomerization. [36] Polymeric biocompatible nanoparticles (NPs) offer advantages as therapeutic agents because they allow modification of surface properties so as to control the adsorption and interaction processes.…”

Section: Introductionmentioning

confidence: 99%

“…[34] The observed effect was interpreted as a result of alterations of the hydration shell of the peptides and hydrophobic effects of fluoro groups. Montserret et al have shown that although the folding in micellar solutions of SDS of hydrophilic, amphipathic a-helical peptides is mostly driven by electrostatic interactions, when hydrophobic peptides are considered, SDS-peptide hydrophobic interactions might be sufficiently strong to bring about the folding process into a a-helical-rich structure.…”

mentioning

confidence: 99%

Controlling Amyloid‐β Peptide(1–42) Oligomerization and Toxicity by Fluorinated Nanoparticles

et al. 2010

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The amyloid-beta peptide (Abeta) is a major fibrillar component of neuritic plaques in Alzheimer's disease brains and is related to the pathogenesis of the disease. Soluble oligomers that precede fibril formation have been proposed as the main neurotoxic species that contributes to neurodegeneration and dementia. We hypothesize that oligomerization and cytotoxicity can be repressed by nanoparticles (NPs) that induce conformational changes in Abeta42. We show here that fluorinated and hydrogenated NPs with different abilities to change Abeta42 conformation influence oligomerization as assessed by atomic force microscopy, immunoblot and SDS-PAGE. Fluorinated NPs, which promote an increase in alpha-helical content, exert an antioligomeric effect, whereas hydrogenated analogues do not and lead to aggregation. Cytotoxicity assays confirmed our hypothesis by indicating that the conformational conversion of Abeta42 into an alpha-helical-enriched secondary structure also has antiapoptotic activity, thereby increasing the viability of cells treated with oligomeric species.

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“…For reasons that are only partially understood, organofl uorine compounds often promote the formation of a -helical structure of peptides, including A b . This is true not only for the familiar solvents 2,2,2-trifluorethanol and 1,1,1,3,3,3-hexafl uoro-2-propanol (Vieira et al 2003 ) , but also solid organofl uorine such poly(tetrafl uoroethylene) surfaces (Giacomelli and Norde 2003 ) . Many of these compounds had some degree of inhibitory activity, and a few of them (e.g., their compound 12, R 1 = R 2 = H, R 3 = F) completely inhibited A b aggregation at high stoichiometric ratios (e.g., 10:1 = inhibitor to A b ), and had IC 50 at substoichiometric ratios to A b below unity.…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 96%

Strategies for Inhibiting Protein Aggregation: Therapeutic Approaches to Protein-Aggregation Diseases

Lanning

Meredith

2011

Non-Fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases

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Self-aggregation of proteins and peptides is at the root of many diseases, especially neurodegenerative diseases. These conditions include Alzheimer's disease, Huntington's disease, Parkinson's disease, type-2 diabetes mellitus, and transmissible spongiform encephalopathies, which are associated with self-aggregation of amyloid b -protein (A b ), huntingtin, a -synuclein, islet amyloid polypeptide, and the prion protein, respectively. The list of diseases for which protein/peptide aggregation is the root cause is ever expanding. There does not appear to be a single biochemical mechanism by which proteins and peptides self-associate, or a single pathogenic mechanism to explain all protein-/peptide-aggregation diseases. Nevertheless, inhibition of protein self-aggregation remains a potential target for therapeutic intervention. Beyond therapy, inhibitors of protein self-aggregation can serve as tools to help us understand the mechanisms by which aggregation occurs and harms cells. In this chapter, we examine select examples of inhibitors of protein aggregation. We have divided aggregating proteins/peptides into two types: (1) Proteins that have an unstable tertiary structure, that unfold under cellular stress, or that fail to fold correctly during biosynthesis. This instability leads to persistence of unfolded domains that can act as a nidus for self-association. (2) Peptides or proteins (or protein domains) that cannot fold at all, or fold only in the presence of a bound ligand. Examples of the fi rst group include transthyretin, the mammalian prion protein, and certain point-mutant forms of lysozyme or a 1-antitrypsin. In general, self-aggregation of these proteins results from exposure of normally buried hydrophobic residues to aqueous media. Examples of the second group include A b , islet amyloid polypeptide, and calcitonin. Within the second group, we also include proteins that are "peptide-like" in having domains with no unique, stable

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Change and stabilization of the amyloid-β(1–40) secondary structure by fluorocompounds

Cited by 54 publications

References 40 publications

The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease

The Role of Amyloid-Beta Derived Diffusible Ligands (ADDLs) in Alzheimers Disease

Controlling Amyloid‐β Peptide(1–42) Oligomerization and Toxicity by Fluorinated Nanoparticles

Strategies for Inhibiting Protein Aggregation: Therapeutic Approaches to Protein-Aggregation Diseases

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