Extracellular interplay of amyloid fibrils and neural cells DOI Creative Commons
Vladimir P. Zhdanov

Biosystems, Год журнала: 2023, Номер 231, С. 104971 - 104971

Опубликована: Июль 8, 2023

Some neurological disorders such e.g. as Alzheimer disease are accompanied by the appearance of amyloid fibrils inside and outside cells. Herein, I present a generic coarse-grained kinetic mean-field model describing at extracellular level interplay It includes formation degradation fibrils, activation healthy cells with respect to fabrication death activated The corresponding analysis indicates that development can occur in two qualitatively different regimes. first one is controlled primarily intrinsic factors resulting slow increase fibril production second implies faster self-promoted growth population analogy explosion. This prediction reported hypothesis interest for conceptual understanding disorders.

Язык: Английский

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
Impact of Amidation on Aβ25–35 Aggregation DOI

Judith C. E. Etaka,

Yan Lü, Wei Kang

и другие.

The Journal of Physical Chemistry B, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Toxic oligomeric species are suspected in the etiology of Alzheimer's disease. The full-length Aβ42 can be studied by fragment Aβ25-35 as it retains neurotoxicity. According to experimental studies, amidation carboxyl terminal decreases fibrillation activity while retaining its neurotoxic properties. Our molecular dynamics simulation aggregation trimer from two initial structures (fibril and randomized helical structures) their amidated nonamidated forms. Comparing systems, results suggest that antiparallel chains dominant amide group leads parallel chains. In terms secondary structures, a higher helix content with corresponding decrease β-sheet is observed consequence amidation. Despite variation chain-chain contacts still mediated Gly motif (GxxxG) Ile residues both systems. As neurotoxicity does not change upon amidation, our imply clumping peptides sustained greater contributing factor toxicity than quaternary structures.

Язык: Английский

Процитировано

0
Peptide Self-Assembly into Amyloid Fibrils: Unbiased All-Atom Simulations DOI
Bradley L. Nilsson, Gizem Çelebi Torabfam, Cristiano L. Dias

и другие.

The Journal of Physical Chemistry B, Год журнала: 2024, Номер 128(14), С. 3320 - 3328

Опубликована: Март 6, 2024

Protein self-assembly plays an important role in biological systems, accounting for the formation of mesoscopic structures that can be highly symmetric as capsid viruses or disordered molecular condensates exhibit a one-dimensional fibrillar morphology amyloid fibrils. Deposits latter tissues individuals with degenerative diseases like Alzheimer's and Parkinson's has motivated extensive efforts to understand sequence events their formation. These studies aim identify on-pathway intermediates may targets therapeutic intervention. This detailed knowledge fibril remains obscure, part due challenges experimental analyses these processes. However, progress is being achieved short peptides advances our ability perform completely unbiased all-atom simulations process. perspective discusses recent developments, implications, hurdles still need overcome further advance field.

Язык: Английский

Процитировано

3
Deciphering the influence of Y12L and N17H substitutions on the conformation and oligomerization of human calcitonin DOI

Jiajia Yan,

Ying Wang,

Xinjie Fan

и другие.

Soft Matter, Год журнала: 2023, Номер 20(3), С. 693 - 703

Опубликована: Дек. 18, 2023

Monomers of hCT primarily adopted dynamic helical structures and readily aggregated into β-sheet-rich oligomers β-barrel intermediates. The Y12L N17H mutations enhanced conformations partially inhibited the helix-to-β conversion.

Язык: Английский

Процитировано

5
Extracellular interplay of amyloid fibrils and neural cells DOI Creative Commons
Vladimir P. Zhdanov

Biosystems, Год журнала: 2023, Номер 231, С. 104971 - 104971

Опубликована: Июль 8, 2023

Some neurological disorders such e.g. as Alzheimer disease are accompanied by the appearance of amyloid fibrils inside and outside cells. Herein, I present a generic coarse-grained kinetic mean-field model describing at extracellular level interplay It includes formation degradation fibrils, activation healthy cells with respect to fabrication death activated The corresponding analysis indicates that development can occur in two qualitatively different regimes. first one is controlled primarily intrinsic factors resulting slow increase fibril production second implies faster self-promoted growth population analogy explosion. This prediction reported hypothesis interest for conceptual understanding disorders.

Язык: Английский

Процитировано

0