Modulation of amyloid-β 1-42 structure and toxicity by proline-rich whey peptides

Bharadwaj, Prashant; Head, Richard; Martins, Ralph N.; Raussens, Vincent; Sarroukh, Rabia; Jegasothy, Hema; Waddington, Lynne J.; Bennett, Louise

doi:10.1039/c2fo30111c

Cited by 21 publications

(20 citation statements)

References 71 publications

(97 reference statements)

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“…The link between antiparallel β structure and oligomer toxicity is more and more documented in literature. For instance, it was shown by ATR-FTIR that whey proline-rich peptides suppressed both oligomerization and the formation of antiparallel β-sheet (Bharadwaj et al, 2013), leading to a rescue of yeast and neuronal cells. Such modulation of the folding pathway of Aβ 1-42 has also been shown for Fucosterol, which protected neuronal cells against Aβ 1-42 -induced toxicity (Gan et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

High Speed AFM and NanoInfrared Spectroscopy Investigation of Aβ1–42 Peptide Variants and Their Interaction With POPC/SM/Chol/GM1 Model Membranes

Feuillie

Lambert

Ewald

et al. 2020

Front. Mol. Biosci.

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Due to an aging population, neurodegenerative diseases such as Alzheimer's disease (AD) have become a major health issue. In the case of AD, Aβ 1-42 peptides have been identified as one of the markers of the disease with the formation of senile plaques via their aggregation, and could play a role in memory impairment and other tragic syndromes associated with the disease. Many studies have shown that not only the morphology and structure of Aβ 1-42 peptide assembly are playing an important role in the formation of amyloid plaques, but also the interactions between Aβ 1-42 and the cellular membrane are crucial regarding the aggregation processes and toxicity of the amyloid peptides. Despite the increasing amount of information on AD associated amyloids and their toxicity, the molecular mechanisms involved still remain unclear and require in-depth investigation at the local scale to clearly decipher the role of the sequence of the amyloid peptides, of their secondary structures, of their oligomeric states, and of their interactions with lipid membranes. In this original study, through the use of Atomic Force Microscopy (AFM) related-techniques, high-speed AFM and nanoInfrared AFM, we tried to unravel at the nanoscale the link between aggregation state, structure and interaction with membranes in the amyloid/membrane interaction. Using three mutants of Aβ peptides, L34T, oG37C, and WT Aβ 1-42 peptides, with differences in morphology, structure and assembly process, as well as model lipidic membranes whose composition and structure allow interactions with the peptides, our AFM study coupling high spatial and temporal resolution and nanoscale structure information clearly evidences a local correlation between the secondary structure of the peptides, their fibrillization kinetics and their interactions with model membranes. Membrane disruption is associated to small transient oligomeric entities in the early stages of aggregation that strongly interact with the membrane, and present an antiparallel β-sheet secondary structure. The strong effect on membrane integrity that exists when these oligomeric Aβ 1-42 peptides interact with membranes of a particular composition could be a lead for therapeutic studies.

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Section: Discussionmentioning

confidence: 99%

High Speed AFM and NanoInfrared Spectroscopy Investigation of Aβ1–42 Peptide Variants and Their Interaction With POPC/SM/Chol/GM1 Model Membranes

Feuillie

Lambert

Ewald

et al. 2020

Front. Mol. Biosci.

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“…These results highlight the major role of the major histocompatibility complex in DIE, whereas additional risk factors for benign eruption may play a role in 6% of the population. In conclusion, for certain drugs and particular populations, screening patients HLA haplotype before drug introduction could be used to reduce DIE occurrence ( 29 ).…”

Section: Pathophysiologymentioning

confidence: 99%

New Insights into Drug Reaction with Eosinophilia and Systemic Symptoms Pathophysiology

Musette

Janela

2017

Front. Med.

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Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is a severe type of cutaneous drug-induced eruption. DRESS may be a difficult disease to diagnose since the symptoms mimic those of cutaneous and systemic infectious pathologies and can appear up to 3 months after the initial culprit drug exposure. The symptoms of DRESS syndrome include rash development after a minimum of 3 weeks after the onset of a new medication, associated with facial edema, lymphadenopathy, and fever. Biological findings include liver abnormalities, leukocytosis, eosinophilia, atypical lymphocytosis, and reactivation of certain human herpes viruses. In DRESS, liver, kidneys, and lungs are frequently involved in disease evolution. Patients with serious systemic involvement are treated with oral corticosteroids, and full recovery is achieved in the majority of cases. DRESS is a rare disease, and little is known about factors that predict its occurrence. The key features of this reaction are eosinophil involvement, the role of the culprit drug, and virus reactivation that trigger an inappropriate systemic immune response in DRESS patients. Interestingly, it was evidenced that at-risk individuals within a genetically restricted population shared a particular HLA loci. In this respect, a limited number of well-known drugs were able to induce DRESS. This review describes the up-to-date advances in our understanding of the pathogenesis of DRESS.

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“…14 Similarly, proline-rich hydrophobic peptides have been found to alter Aβ 1-42 folding and fibril formation. 20 . Seminal work in AD indicated that tachykinin neuropeptides possess the ability to ameliorate the neurotoxic effects of Aβ peptides.…”

Section: Introductionmentioning

confidence: 99%

Amyloid-β–neuropeptide interactions assessed by ion mobility-mass spectrometry

Soper

DeToma

Hyung

et al. 2013

Phys. Chem. Chem. Phys.

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Recently, small peptides have been shown to modulate aggregation and toxicity of the amyloid-β protein (Aβ). As such, these new scaffolds may help discover a new class of biotherapeutics useful in the treatment of Alzheimer's disease. Many of these inhibitory peptide sequences have been derived from natural sources or from Aβ itself (e.g., C-terminal Aβ fragments). In addition, much earlier work indicates that tachykinins, a broad class of neuropeptides, display neurotrophic properties, presumably through direct interactions with either Aβ or its receptors. Based on this work, we undertook a limited screen of neuropeptides using ion mobility-mass spectrometry to search for similar such peptides with direct Aβ binding properties. Our results reveal that the neuropeptides leucine enkephalin (LE) and galanin interact with both the monomeric and small oligomeric forms of Aβ1-40 to create a range of complexes having diverse stoichiometries, while some tachyknins (i.e., substance P) do not. LE interacts with Aβ more strongly than galanin, and we utilized ion mobility-mass spectrometry, molecular dynamics simulations, gel electrophoresis/Western blot, and transmission electron microscopy to study the influence of this peptide on the structure of Aβ monomer, small Aβ oligomers, as well as the eventual formation of Aβ fibrils. We find that LE binds selectively within a region of Aβ between its N-terminal tail and hydrophobic core. Furthermore, our data indicate that LE modulates fibril generation, producing shorter fibrillar aggregates when added in stoichiometric excess relative to Aβ.

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Modulation of amyloid-β 1-42 structure and toxicity by proline-rich whey peptides

Cited by 21 publications

References 71 publications

High Speed AFM and NanoInfrared Spectroscopy Investigation of Aβ1–42 Peptide Variants and Their Interaction With POPC/SM/Chol/GM1 Model Membranes

High Speed AFM and NanoInfrared Spectroscopy Investigation of Aβ1–42 Peptide Variants and Their Interaction With POPC/SM/Chol/GM1 Model Membranes

New Insights into Drug Reaction with Eosinophilia and Systemic Symptoms Pathophysiology

Amyloid-β–neuropeptide interactions assessed by ion mobility-mass spectrometry

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