Exploring the Curvature-Dependence of Boron Nitride Nanoparticles on the Inhibition of hIAPP Aggregation DOI
Rituparna Roy, Sandip Paul

The Journal of Physical Chemistry B, Journal Year: 2023, Volume and Issue: 127(35), P. 7558 - 7570

Published: Aug. 24, 2023

Nanoparticles, particularly carbon nanoparticles, have gathered significant interest in the field of anti-aggregation research. However, due to their cytotoxicity, exploration biocompatible nanoparticles has become a new frontier quest for drugs against human amyloid diseases. The application non-cytotoxic and boron nitride (BN) aggregation been probed tackle this issue. BN displayed inhibitory activity Aβ α-syn peptides. In work, effect on dimerization hIAPP, which is associated with pathogenesis type 2 diabetes, studied. prevent misfolding hIAPP into β-sheet-rich aggregates. On varying curvature, display variation interaction preference hIAPP. Interestingly, as hydrophobicity increases from (5,5) nanotube nanosheet, propensity shifts N-terminal prone C-terminal hydrophobic aromatic stacking interactions are contributing factor toward binding between BN. Due this, flat surface nanosheet shows better potential compared nanotubes. Further, can also disassemble preformed fibrils, more pronounced nanosheet. This study provides insight mechanism by an understanding significance curvature peptides, valuable design antiamyloid drugs.

Language: Английский

A unifying framework for amyloid-mediated membrane damage: The lipid-chaperone hypothesis DOI
Carmelo Tempra, Federica Scollo, Martina Pannuzzo

et al.

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Journal Year: 2022, Volume and Issue: 1870(4), P. 140767 - 140767

Published: Feb. 8, 2022

Language: Английский

Citations

23
Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus DOI Creative Commons

Wenhao Fu,

Huanyu Chi,

Xin Dai

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 2, 2023

It is challenging to characterize single or a few biomolecules in physiological milieus without excluding the influences of surrounding environment. Here we utilize optical plasmonic trapping construct dynamic nanocavity, which reduces diffraction-limited detection volume and provides reproducible electromagnetic field enhancements achieve high-throughput single-molecule surface-enhanced Raman spectroscopy (SERS) characterizations aqueous environments. Specifically, study human Islet Amyloid Polypeptide (amylin, hIAPP) under different pH conditions by combining spectroscopic experiments molecular dynamics (MD) simulations. Based on statistically significant amount time-dependent SERS spectra, two types low-populated transient species hIAPP containing either turn β-sheet structure among its predominant helix-coil monomers are characterized during early-stage incubation at neutral condition, play crucial role driving irreversible amyloid fibril developments even after subsequent adjustment continue prolonged acidic condition. Our results might provide profound mechanistic insight into pH-regulated amyloidogenesis introduce an alternative approach for investigating complex biological processes level.

Language: Английский

Citations

16
Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena DOI Creative Commons

Faisal Alanazi,

Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Journal of Diabetes, Journal Year: 2023, Volume and Issue: 15(5), P. 397 - 408

Published: April 19, 2023

Abstract Neprilysin (NEP) is a transmembrane zinc‐dependent metalloproteinase that inactivates various peptide hormones including glucagon‐like 1 (GLP‐1). NEP inhibitors may be effective in the management of type 2 diabetes mellitus (T2DM) by increasing circulating level GLP‐1. However, acute‐effect lead to detrimental effects blood glucose independent These findings suggest controversial point regarding potential role on homeostasis T2DM patients. Therefore, this perspective aimed clarify points concerning T2DM. beneficial inhibition NEP, which involved impairment through modulation insulin resistance. increases dipeptidyl peptidase‐4 (DPP4) activity and contributes active GLP‐1 proteolysis so improve glycemic control endogenous reduction DPP4 activity. Thus, could alone or combination with antidiabetic agents treating long‐term short‐term effect sensitivity different mechanisms augmentation substrates pancreatic amyloid deposition. are confirmed animal but not humans. In conclusion, produce rather than humans though most studies.

Language: Английский

Citations

15
Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation DOI Open Access

Avisek Bera,

Pooja Ghosh, Shilpendu Ghosh

et al.

Macromolecular Bioscience, Journal Year: 2023, Volume and Issue: 23(7)

Published: April 24, 2023

Lipoic acid (LA) and dihydrolipoic (DHLA) are well established antioxidants to scavenge reactive oxygen species (ROS). However, they carboxylates with ≈4.7 pKa making them negatively charged at physiological pH (7.4) reducing their passive diffusion through cell membranes. LA is known be capable of protein fibrillation. Incorporation especially DHLA in polymer side chains scarce. Herein, the first examples anti-amyloidogenic effect incorporated into side-chain a block copolymer water-soluble poly(polyethylene glycol methyl ether methacrylate) (PPEGMA) segment presented. The resultant polymers show improved ROS scavenging activity ability reduce insulin fibrillation compared free DHLA. Furthermore, also disintegrating preformed firbrils. Interestingly, dihydro-lipoate moieties showed 93% radical 91% anti-fibrillating efficacies for confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay Thioflavin T (ThT) dye binding study, respectively. Further, antioxidant increase viability against fibrillar aggregates that may involved etiology several diseases. Overall, this work reveals polymer-based therapeutic agents can serve as powerful modulation strategy developing novel drugs future amyloid-related disorders.

Language: Английский

Citations

13
Exploring the Curvature-Dependence of Boron Nitride Nanoparticles on the Inhibition of hIAPP Aggregation DOI
Rituparna Roy, Sandip Paul

The Journal of Physical Chemistry B, Journal Year: 2023, Volume and Issue: 127(35), P. 7558 - 7570

Published: Aug. 24, 2023

Nanoparticles, particularly carbon nanoparticles, have gathered significant interest in the field of anti-aggregation research. However, due to their cytotoxicity, exploration biocompatible nanoparticles has become a new frontier quest for drugs against human amyloid diseases. The application non-cytotoxic and boron nitride (BN) aggregation been probed tackle this issue. BN displayed inhibitory activity Aβ α-syn peptides. In work, effect on dimerization hIAPP, which is associated with pathogenesis type 2 diabetes, studied. prevent misfolding hIAPP into β-sheet-rich aggregates. On varying curvature, display variation interaction preference hIAPP. Interestingly, as hydrophobicity increases from (5,5) nanotube nanosheet, propensity shifts N-terminal prone C-terminal hydrophobic aromatic stacking interactions are contributing factor toward binding between BN. Due this, flat surface nanosheet shows better potential compared nanotubes. Further, can also disassemble preformed fibrils, more pronounced nanosheet. This study provides insight mechanism by an understanding significance curvature peptides, valuable design antiamyloid drugs.

Language: Английский

Citations

13