Structure of amyloid oligomers and their mechanisms of toxicities: Targeting amyloid oligomers using novel therapeutic approaches

Salahuddin, Parveen; Fatima, Mahvish; Abdelhameed, Ali S.; Nusrat, Saima; Khan, Rizwan Hasan

doi:10.1016/j.ejmech.2016.02.065

Cited by 82 publications

(60 citation statements)

References 250 publications

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“…Structural information about amyloid oligomers is important for better understanding of their pathological roles in the disease and for development of therapeutic agents that block oligomers from propagating from cell to cell by preventing their entry into cells, dissociate their toxic secondary structures, or by inhibiting further polymerization with endogenous soluble Aβ [8,9].…”

Section: Introductionmentioning

confidence: 99%

Structural differences between amyloid beta oligomers

Breydo

Kurouski

Rasool

et al. 2016

Biochemical and Biophysical Research Communications

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Section: Introductionmentioning

confidence: 99%

Structural differences between amyloid beta oligomers

Breydo

Kurouski

Rasool

et al. 2016

Biochemical and Biophysical Research Communications

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“…Antibody‐based candidates that target Aβ oligomers have generated encouraging preliminary results (Salahuddin et al . ; Sevigny et al . ), but the high manufacturing and distribution costs of such biologics have raised concerns over their general accessibility.…”

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confidence: 99%

Label‐free distribution of anti‐amyloid D‐AIP in Drosophila melanogaster: prevention of Aβ42‐induced toxicity without side effects in transgenic flies

Zhong

Shobo

Hancock

et al. 2019

Journal of Neurochemistry

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Soluble oligomers of the 42‐amino acid amyloid beta (Aβ42) peptide are highly toxic and suspected as the causative agent of synaptic dysfunction and neuronal loss in Alzheimer's disease (AD). Previously, we have shown that a small, D‐amino acid Aβ42‐oligomer interacting peptide (D‐AIP) can neutralize human Aβ42‐mediated toxicity using in vitro and cell‐based assays. In the present longitudinal study using a transgenic Drosophila melanogaster model, advanced live confocal imaging and mass spectrometry imaging (MALDI‐MSI) showed that the eight amino acid D‐AIP can attenuate Aβ42‐induced toxicity in vivo. By separating male and female flies into distinct groups, the resultant distribution of ingested D‐AIP was different between the sexes. The Aβ42‐induced ‘rough eye’ phenotype could be rescued in the female transgenics, likely because of the co‐localization of D‐AIP with human Aβ42 in the female fly heads. Interestingly, the phenotype could not be rescued in the male transgenics, likely because of the co‐localization of D‐AIP with a confounding male‐specific sex peptide (Acp70A candidate in MSI spectra) in the gut of the male flies. As a novel, more cost‐effective strategy to prevent toxic amyloid formation during the early stages of AD (i.e. neutralization of toxic low‐order Aβ42 oligomers without creating larger aggregates in the process), our longitudinal study establishes that D‐AIP is a stable and highly effective neutralizer of toxic Aβ42 peptides in vivo. Cover Image for this issue: doi: .

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“…In its native state, human α-synuclein is largely unfolded. Through a nucleation polymerization mechanism, involving major structural rearrangements, α-synuclein transforms into different, transient prefibrillar species that vary in size and morphology [8]. Despite the assistance of molecular chaperones during protein folding, protein misfolding is inevitable because of changes in the environment and various other factors, including errors in post-translational modifications, an increase in the rate of degradation, and errors in trafficking.…”

Section: The Toxicities Of Different Structures Of α-Synucleinmentioning

confidence: 99%

“…Despite the assistance of molecular chaperones during protein folding, protein misfolding is inevitable because of changes in the environment and various other factors, including errors in post-translational modifications, an increase in the rate of degradation, and errors in trafficking. When the misfolded protein interacts with complementary intermediates, the pathway of amyloid fibril formation from monomers to oligomers, and consequently mature fibrils, is initiated [8]. …”

Section: The Toxicities Of Different Structures Of α-Synucleinmentioning

confidence: 99%

Structure, Distribution, and Genetic Profile of α-Synuclein and Their Potential Clinical Application in Parkinson’s Disease

Zhang

2017

JMD

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Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy.

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Structure of amyloid oligomers and their mechanisms of toxicities: Targeting amyloid oligomers using novel therapeutic approaches

Cited by 82 publications

References 250 publications

Structural differences between amyloid beta oligomers

Structural differences between amyloid beta oligomers

Label‐free distribution of anti‐amyloid D‐AIP in Drosophila melanogaster: prevention of Aβ42‐induced toxicity without side effects in transgenic flies

Structure, Distribution, and Genetic Profile of α-Synuclein and Their Potential Clinical Application in Parkinson’s Disease

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