Structure of ring-shaped Aβ42 oligomers determined by conformational selection

Tran, Linh; Basdevant, Nathalie; Prévost, Chantal; Ha-Duong, Tâp

doi:10.1038/srep21429

Cited by 34 publications

(35 citation statements)

References 87 publications

(125 reference statements)

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“…45 C a RMSD and R g were chosen as the coordinates as they were successfully used to obtain the FEL for other Ab peptide systems. [61][62][63] The FEL of solvated D23N 3Ab 11-40 is displayed in Fig. 5, which contains four minima centered at (RMSD; R g ) coordinates of (0.48; The selected structural parameters of these conformations are provided in Table 1.…”

Section: Free Energy Landscapementioning

confidence: 99%

Atomistic investigation of an Iowa Amyloid-β trimer in aqueous solution

Ngo

Phung

et al. 2018

RSC Adv.

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Section: Free Energy Landscapementioning

confidence: 99%

Atomistic investigation of an Iowa Amyloid-β trimer in aqueous solution

Ngo

Phung

et al. 2018

RSC Adv.

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“…However, completely determining the structure of Aβ oligomers and elucidating their aggregation process still remain challenging because of fast aggregation, flexibility and heterogeneous ensemble of the Aβ oligomers [ 11 ]. As a complement to the experimental methods, computer simulation methods can provide the detailed information on the structural features of the Aβ oligomers at the atomic level [ 12 ]. They are also applied to explore the aggregated forms of the Aβ oligomers embedded within the lipid membrane [ 13 ] and investigate their effects on the membrane [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Study of structural stability and damaging effect on membrane for four Aβ42 dimers

Feng

Lei

et al. 2017

PLoS ONE

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Increasing evidence shows that Aβ oligomers are key pathogenic molecules in Alzheimer’s disease. Among Aβ oligomers, dimer is the smallest aggregate and toxic unit. Therefore, understanding its structural and dynamic properties is quite useful to prevent the formation and toxicity of the Aβ oligomers. In this study, we performed molecular dynamic simulations on four Aβ42 dimers, 2NCb, CNNC, NCNC and NCCN, within the hydrated DPPC membrane. Four Aβ42 dimers differ in the arrangements of two Aβ42 peptides. This study aims to investigate the impact of aggregation pattern of two Aβ peptides on the structural stability of the Aβ42 dimer and its disruption to the biological membrane. The MD results demonstrate that the NCCN, CNNC and NCNC have the larger structural fluctuation at the N-terminus of Aβ42 peptide, where the β-strand structure converts into the coil structure. The loss of the N-terminal β-strand further impairs the aggregate ability of Aβ42 dimer. In addition, inserting Aβ42 dimer into the membrane can considerably decrease the average APL of DPPC membrane. Moreover this decrease effect is largely dependent on the distance to the location of Aβ42 dimer and its secondary structure forms. Based on the results, the 2NCb is considered as a stable dimeric unit for aggregating the larger Aβ42 oligomer, and has a potent ability to disrupt the membrane.

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“…The soluble peptide has no alpha-helical or beta-sheet character but adopts a collapsed coil structure [80] . A particular conformation that forms ring-shaped pentamers and hexamers is stable by microsecond all-atom MD simulations [81] . The relationship between oligomers and fibrils remains to be established.…”

Section: Aβ Oligomersmentioning

confidence: 99%

Amyloid beta: structure, biology and structure-based therapeutic development

et al. 2017

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Amyloid beta peptide (Aβ) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β-and γ-secretases. Aβ accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of Aβ are and by what mechanism Aβ causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease. In this paper, we review the structures, biological functions, and neurotoxicity role of Aβ. We also discuss the potential receptors that interact with Aβ and mediate Aβ intake, clearance, and metabolism. Additionally, we summarize the therapeutic developments and recent advances of different strategies for treating Alzheimer's disease. Finally, we will report on the progress in searching for novel, potentially effective agents as well as selected promising strategies for the treatment of Alzheimer's disease. These prospects include agents acting on Aβ, its receptors and tau protein, such as small molecules, vaccines and antibodies against Aβ; inhibitors or modulators of β-and γ-secretase; Aβ-degrading proteases; tau protein inhibitors and vaccines; amyloid dyes and microRNAs.

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Structure of ring-shaped Aβ42 oligomers determined by conformational selection

Cited by 34 publications

References 87 publications

Atomistic investigation of an Iowa Amyloid-β trimer in aqueous solution

Atomistic investigation of an Iowa Amyloid-β trimer in aqueous solution

Study of structural stability and damaging effect on membrane for four Aβ42 dimers

Amyloid beta: structure, biology and structure-based therapeutic development

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