Effect of Cholesterol Molecules on Aβ1-42 Wild-Type and Mutants Trimers DOI Creative Commons
Trung Hai Nguyen, Phuong H. Nguyen,

Sơn Tùng Ngô

и другие.

Molecules, Год журнала: 2022, Номер 27(4), С. 1395 - 1395

Опубликована: Фев. 18, 2022

Alzheimer's disease displays aggregates of the amyloid-beta (Aβ) peptide in brain, and there is increasing evidence that cholesterol may contribute to pathogenesis disease. Though many experimental theoretical studies have focused on interactions Aβ oligomers with membrane models containing cholesterol, an understanding effect free small Aβ42 not fully established. To address this question, we report replica exchange a solute tempering simulation trimer compare it previous molecular dynamics simulation. We show binding hot spots are rather complex, involving hydrophobic residues L17-F20 L30-M35 non-negligible contribution loop D22-K28 N-terminus residues. also examine effects trimers disease-causing A21G disease-protective A2T mutations by simulations. these two moderately impact cholesterol-binding modes. In our REST2 simulations, find rarely inserted into but attached as dimers at surface oligomers. propose acts glue speed up formation larger aggregates; provides mechanistic link between

Язык: Английский

LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases DOI Creative Commons

Surajit Bhattacharjya,

Zhizhuo Zhang,

Ayyalusamy Ramamoorthy

и другие.

Biomolecules, Год журнала: 2024, Номер 14(3), С. 320 - 320

Опубликована: Март 8, 2024

Antimicrobial peptides (AMPs), as well host defense (HDPs), constitute the first line of part innate immune system. Humans are known to express antimicrobial precursor proteins, which further processed generate AMPs, including several types α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity is crucial defend against infections caused by pathogenic bacteria, viruses, fungi, parasites. emergence multi-drug resistant bacteria global concern for public health. prospects targeting antibiotic-resistant strains with high significance developing new generations agents. 37-residue long LL37, only cathelicidin family AMP in humans, has been major focus past few decades research. LL37 likely underscored its expression throughout body, spanning from epithelial cells various organs—testis, skin, respiratory tract, gastrointestinal tract—to cells. Remarkably, apart canonical direct killing organisms, exerts other activities, inflammatory response modulation, chemo-attraction, wound healing closure at infected sites. In addition, derived bestowed anti-cancer anti-amyloidogenic properties. this review article, we aim develop integrative, mechanistic insight into peptides, based on biophysical, structural, functional studies recent years. We believe that will pave way future research structures, biochemical biophysical properties, design novel LL37-based molecules.

Язык: Английский

Процитировано

28
Drug delivery of memantine with carbon dots for Alzheimer’s disease: blood–brain barrier penetration and inhibition of tau aggregation DOI Creative Commons
Wei Zhang,

Nabin Kandel,

Yiqun Zhou

и другие.

Journal of Colloid and Interface Science, Год журнала: 2022, Номер 617, С. 20 - 31

Опубликована: Март 1, 2022

Язык: Английский

Процитировано

67
Intrinsically disordered proteins/regions and insight into their biomolecular interactions DOI
Pinak Chakrabarti, Devlina Chakravarty

Biophysical Chemistry, Год журнала: 2022, Номер 283, С. 106769 - 106769

Опубликована: Фев. 1, 2022

Язык: Английский

Процитировано

59
A Hairpin Motif in the Amyloid-β Peptide Is Important for Formation of Disease-Related Oligomers DOI Creative Commons
Mohammed Khaled,

Isabel Rönnbäck,

Leopold L. Ilag

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(33), С. 18340 - 18354

Опубликована: Авг. 9, 2023

The amyloid-β (Aβ) peptide is associated with the development of Alzheimer's disease and known to form highly neurotoxic prefibrillar oligomeric aggregates, which are difficult study due their transient, low-abundance, heterogeneous nature. To obtain high-resolution information about oligomer structure dynamics as well relative populations assembly states, we here employ a combination native ion mobility mass spectrometry molecular simulations. We find that formation Aβ oligomers dependent on presence specific β-hairpin motif in sequence. Oligomers initially grow spherically but start extended linear aggregates at states larger than those tetramer. population could be notably increased by introducing an intramolecular disulfide bond, prearranges hairpin conformation, thereby promoting structures preventing conversion into mature fibrils. Conversely, truncating one β-strand-forming segments decreased propensity thus population, removed entirely, aggregation peptide. propose observed state related antiparallel sheet state, then nucleates amyloid state. These studies provide mechanistic understanding earliest steps suggest inhibition folding conformation viable strategy for reducing amount toxic oligomers.

Язык: Английский

Процитировано

38
A brief history of amyloid aggregation simulations DOI
Hebah Fatafta, Mohammed Khaled, Batuhan Kav

и другие.

Wiley Interdisciplinary Reviews Computational Molecular Science, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 1, 2024

Abstract Amyloid proteins are characterized by their tendency to aggregate into amyloid fibrils, which often associated with devastating diseases. Aggregation pathways typically involve unfolding or misfolding of monomeric and formation transient oligomers protofibrils before the final aggregation product is formed. The conformational dynamics polymorphic volatile nature these intermediates make characterization experimental techniques alone insufficient also require computational approaches. Over past 25 years, size simulated systems length simulations have increased significantly. These advances discussed here. review includes simulation approaches that model aggregating peptides at both all‐atom coarse‐grained levels, use molecular Monte Carlo sampling simulate changes, present results for various ranging from Lys‐Phe‐Phe‐Glu (KFFE) as smallest system an intermediate‐sized peptide α‐synuclein. presentation history concludes a discussion where future may lie. This article categorized under: Structure Mechanism > Computational Biochemistry Biophysics Molecular Statistical Mechanics Dynamics Monte‐Carlo Methods

Язык: Английский

Процитировано

10
Molecular insights into the phase transition of lysozyme into amyloid nanostructures: Implications of therapeutic strategies in diverse pathological conditions DOI

Sindhujit Roy,

Venkat Ramanan Srinivasan,

Subash Arunagiri

и другие.

Advances in Colloid and Interface Science, Год журнала: 2024, Номер 331, С. 103205 - 103205

Опубликована: Май 23, 2024

Язык: Английский

Процитировано

10
Revolution in Cancer Treatment Methods: Perspective Review of Factors Affecting the Final Results of Nanoparticles Used in Magnetic Fluid Hyperthermia DOI Creative Commons

parisa oskoui,

Maryam Rezvani

Health Sciences Review, Год журнала: 2025, Номер unknown, С. 100212 - 100212

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2
A mechanistic survey of Alzheimer's disease DOI Creative Commons
Yijing Tang, Dong Zhang, Xiong Gong

и другие.

Biophysical Chemistry, Год журнала: 2021, Номер 281, С. 106735 - 106735

Опубликована: Ноя. 30, 2021

Язык: Английский

Процитировано

45
Amyloid β interaction with model cell membranes – What are the toxicity-defining properties of amyloid β? DOI Creative Commons
Dušan Mrđenović, Izabela S. Pieta, Robert Nowakowski

и другие.

International Journal of Biological Macromolecules, Год журнала: 2022, Номер 200, С. 520 - 531

Опубликована: Янв. 21, 2022

Disruption of the neuronal membrane by toxic amyloid β oligomers is hypothesized to be major event associated with Alzheimer's disease's neurotoxicity. Misfolding followed aggregation via different pathways in which structurally can formed. The respective actions these diverse vary significantly. Linking a particular action unique kind and resolving their toxicity-determining feature remains challenging because transient stability heterogeneity. Moreover, lipids that make up affect oligomers' behavior, thus adding problem's complexity. present review compares analyzes latest results improve understanding interaction lipid bilayers.

Язык: Английский

Процитировано

34
Molecular insight into cross-interaction between amyloid β isoforms and its effect on aggregation pathways DOI
Li Wang, Sanghwan Park, Jae Hong Choi

и другие.

Journal of Biomolecular Structure and Dynamics, Год журнала: 2025, Номер unknown, С. 1 - 11

Опубликована: Март 7, 2025

The self-aggregation of amyloid β (Aβ) proteins has played a crucial role in the pathogenesis Alzheimer's diseases. Despite previous studies on aggregation process Aβ proteins, little is known about how cross-interaction between isoforms affects pathways and resulting structures aggregates. Here, we study Aβ40 Aβ42 during their by measuring kinetics aggregates under varied concentrations isoform mixture. We found that mixture monomers results concentration-dependent leading to different aggregate such way induce structural types as sized oligomers or fibrils with morphologies flexibilities. Moreover, investigate effect (or Aβ42) oligomer fibril seeds pathway Aβ40). show fibril) seed not only but also Our sheds light at primary nucleation level its pathways.

Язык: Английский

Процитировано

1