Pore Formation by Amyloid-like Peptides: Effects of the Nonpolar–Polar Sequence Pattern DOI
Warin Rangubpit,

Siwaporn Sungted,

Jirasak Wong-ekkabut

и другие.

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(18), С. 3354 - 3362

Опубликована: Авг. 22, 2024

One of the mechanisms accounting for toxicity amyloid peptides in diseases like Alzheimer's and Parkinson's is formation pores on plasma membrane neurons. Here, we perform unbiased all-atom simulations full damaging pathway, which includes adsorption, aggregation, perforation lipid bilayer pore-like structures. Simulations are performed using four made with same amino acids. Differences nonpolar–polar sequence pattern these prompt them to adsorb into extended conformations oriented either parallel [peptide labeled F1, Ac-(FKFE)2-NH2], perpendicular (F4, Ac-FFFFKKEE-NH2), or an intermediate orientation (F2, Ac-FFKKFFEE-NH2, F3, Ac-FFFKFEKE-NH2) regard surface. At water–lipid interface, only F1 fully self-assembles β-sheets, F2 partially fold α-helical structure. The β-sheets emerge as electrostatic interactions attract neighboring distances where nonpolar side chains can interact within dry core bilayer. This complex interplay between not observed other peptides. Although mostly membrane, some their edges penetrate deep inside bilayer, dragging water molecules them. precedes pore formation, starts flow two layers through that expand a stable cylindrical delimited by polar faces spanning both leaflets

Язык: Английский

Therapeutic Advantages of Nanoparticle-Impregnated Lysozyme Conjugates toward Amyloid-β Fibrillation and Antimicrobial Activity DOI

Jahnabi Upadhyaya,

Imocha Rajkumar Singh, Bishal Pun

и другие.

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

Опубликована: Янв. 15, 2025

The interaction of protein with nanoparticles (NPs) varying shape and/or size boosts our understanding on their bioreactivity and establishes a comprehensive database for use in medicine, diagnosis, therapeutic applications. present study explores the between lysozyme (LYZ) different NPs like graphene oxide (GO) zinc (ZnO) having various shapes (spherical, 's', rod-shaped, 'r') sizes, focusing binding dynamics subsequent effects both fibrillation antimicrobial properties. Typically, GO is considered promising medium due to its apparent inhibition prolonged lag phase LYZ fibrillation. However, results showed that spherical ZnO (sZnO) offer superior efficacy modulating an extended time about 158.70 h, further emphasizing importance detailed investigation nanomaterial characteristics fibril formation kinetics beyond initial observations. experimental findings confirmed strong correlation affinity native effective denaturation, ultimately preventing formation. Interestingly, nanoconjugates intriguing bactericidal effects, as through agar plate assay SEM imaging, over protein. Overall, this shows appropriate bionanomaterials can exhibit multifunctional properties, which paves way deeper NP characteristics, benefiting wide array research.

Язык: Английский

Процитировано

0

Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids DOI Creative Commons
Doris Loh, Russel J. Reíter

Exploration of neuroscience, Год журнала: 2025, Номер 4

Опубликована: Март 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Язык: Английский

Процитировано

0

Pore Formation by Amyloid-like Peptides: Effects of the Nonpolar–Polar Sequence Pattern DOI
Warin Rangubpit,

Siwaporn Sungted,

Jirasak Wong-ekkabut

и другие.

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(18), С. 3354 - 3362

Опубликована: Авг. 22, 2024

One of the mechanisms accounting for toxicity amyloid peptides in diseases like Alzheimer's and Parkinson's is formation pores on plasma membrane neurons. Here, we perform unbiased all-atom simulations full damaging pathway, which includes adsorption, aggregation, perforation lipid bilayer pore-like structures. Simulations are performed using four made with same amino acids. Differences nonpolar–polar sequence pattern these prompt them to adsorb into extended conformations oriented either parallel [peptide labeled F1, Ac-(FKFE)2-NH2], perpendicular (F4, Ac-FFFFKKEE-NH2), or an intermediate orientation (F2, Ac-FFKKFFEE-NH2, F3, Ac-FFFKFEKE-NH2) regard surface. At water–lipid interface, only F1 fully self-assembles β-sheets, F2 partially fold α-helical structure. The β-sheets emerge as electrostatic interactions attract neighboring distances where nonpolar side chains can interact within dry core bilayer. This complex interplay between not observed other peptides. Although mostly membrane, some their edges penetrate deep inside bilayer, dragging water molecules them. precedes pore formation, starts flow two layers through that expand a stable cylindrical delimited by polar faces spanning both leaflets

Язык: Английский

Процитировано

0