Influence of oxodiperoxovanadate complexes on prion neuropeptide fibril formation

Zhang, Baohong; Zhu, Dengsen; Gong, Gehui; Du, Weihong

doi:10.1039/c5ra25849a

Cited by 8 publications

(2 citation statements)

References 65 publications

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“…Artemisinin and its derivatives have great antimalarial activities based on the interaction of the compound with hemin . ESI-MS is a powerful tool in exploring the interaction between the inhibitors and peptides. , The two peptides alone emerged with a single peak at 3903 ± 1 and 4514 ± 1, which matched the expected mass of hIAPP and Aβ (data not shown). The formation of adduct peaks was observed after adding these artemisinin compounds (Figures and ).…”

Section: Resultsmentioning

confidence: 94%

Regulation of Artemisinin and Its Derivatives on the Assembly Behavior and Cytotoxicity of Amyloid Polypeptides hIAPP and Aβ

Zhao

Huang

et al. 2019

ACS Chem. Neurosci.

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The misfolding and aggregation of human islet amyloid polypeptide (hIAPP) and amyloid-β (Aβ) protein are closely associated with type 2 diabetes mellitus (T2DM) and Alzheimer’s disease, respectively. Inhibitors of amyloid peptides include short peptides, aromatic organic molecules, nanoparticles, and even metal compounds. Sesquiterpenoid artemisinins are widely used in anti-malaria treatments, and they may modulate glucose homeostasis against diabetes. However, the antidiabetic mechanism of these compounds remains unclear. In this work, four compounds, namely, artemisinin (1), dihydroartemisinin (2), artesunate (3), and artemether (4), were exploited to inhibit the assembly behavior of hIAPP and compared with that of Aβ. Although structurally distinct from other aromatic inhibitors of amyloid peptides, these sesquiterpenoids effectively altered the two peptides’ fibril morphologies and disaggregated the mature fibrils mostly to the monomers. The interaction of artemisinins with the two peptides demonstrated a spontaneous, exothermic, and entropy-driven binding process predominantly through hydrophobic and hydrogen bonding interactions. Moreover, they reversed cytotoxicity and membrane leakage by reducing peptides’ oligomerization. The results suggested that these compounds had better inhibition and disaggregation capability against hIAPP than against Aβ. Furthermore, the effects of these compounds’ structural modification on the amyloid fibril formation of the two peptides were observed. The molecular screening offered a new perspective for artemisinins as promising inhibitors against amyloidosis related diseases.

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Section: Resultsmentioning

confidence: 94%

Regulation of Artemisinin and Its Derivatives on the Assembly Behavior and Cytotoxicity of Amyloid Polypeptides hIAPP and Aβ

Zhao

Huang

et al. 2019

ACS Chem. Neurosci.

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“…Prion diseases, including Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, bovine spongiform encephalopathy, and scrapie, affect the cognition and behavior pattern of humans and other mammals. − Cellular prion protein (PrP C ) is a widespread glycoprotein anchored to the plasma membrane of cells with the help of glycosylphosphatidylinositol and is highly conserved in mammalian cells . The abnormal conformational transition of PrP C to scrapie prion protein (PrP Sc ) is thought to be a crucial infectious path of prion disorders. ,, The two isomers have different secondary structures, which leads to their different physicochemical properties. Compared to PrP C , PrP Sc has more β-sheets and fewer α-helix structures, and the self-assembly and accumulation of PrP Sc in the central nervous system of infected individuals cause neuronal cell death or dysfunction. , …”

Section: Introductionmentioning

confidence: 99%

Roles of Apigenin and Nepetin in the Assembly Behavior and Cytotoxicity of Prion Neuropeptide PrP106-126

Huo,

Zhao,

Wang

et al. 2023

ACS Chem. Neurosci.

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Development of potential inhibitors to prevent prion protein (PrP) fibrillation is a therapeutic strategy for prion diseases. The prion neuropeptide PrP106-126, a research model of abnormal PrP (PrP Sc ), presents similar physicochemical and biochemical characters to PrP Sc , which is also a target of potential inhibitors against prion deposition. Many flavones have antioxidant, anti-inflammatory, and antibacterial properties, and they are applied in treating prion disorder and other amyloidosis as well. However, the inhibition mechanism of flavones on PrP106-126 fibrillation is still unclear. In the current work, apigenin and nepetin were used to suppress the aggregation of PrP106-126 and to alleviate the peptide-induced cytotoxicity. The results showed that apigenin and nepetin impeded the fibril formation of PrP106-126 and depolymerized the preformed fibrils. They were bound to PrP106-126 predominantly by hydrophobic and hydrogen bonding interactions. In addition, both flavones upregulated cell viability and decreased membrane leakage through reducing peptide oligomerization. The differences in inhibition and cell protection between the two small molecules were presumably attributed to the substitution of hydroxyl and methoxy groups in nepetin, which demonstrated the significant structure−function relationship of flavones with prion neuropeptide and the prospect of flavonoids as drug candidates against prion diseases.

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Transition Metal Complexes as Therapeutics: A New Frontier in Combatting Neurodegenerative Disorders through Protein Aggregation Modulation

Navale,

Ahmed,

Lim

et al. 2024

Adv Healthcare Materials

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Neurodegenerative disorders (NDDs) are a class of debilitating diseases that progressively impair the protein structure and result in neurological dysfunction in the nervous system. Among these disorders, Alzheimer's disease (AD), prion diseases such as Creutzfeldt‐Jakob disease (CJD), and Parkinson's disease (PD) are caused by protein misfolding and aggregation at the cellular level. In recent years, transition metal complexes have gained significant attention for their potential applications in diagnosing, imaging, and curing these NDDs. These complexes have intriguing possibilities as therapeutics due to their diverse ligand systems and chemical properties and can interact with biological systems with minimal detrimental effects. This review focuses on the recent progress in transition metal therapeutics as a new era of hope in the battle against AD, CJD, and PD by modulating protein aggregation in vitro and in vivo. It may shed revolutionary insights into unlocking new opportunities for researchers to develop metal‐based drugs to combat NDDs.

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Influence of oxodiperoxovanadate complexes on prion neuropeptide fibril formation

Abstract: Different oxodiperoxovanadate complexes inhibit the fibril formation of prion neuropeptides by different action modes.

Cited by 8 publications

References 65 publications

Regulation of Artemisinin and Its Derivatives on the Assembly Behavior and Cytotoxicity of Amyloid Polypeptides hIAPP and Aβ

Regulation of Artemisinin and Its Derivatives on the Assembly Behavior and Cytotoxicity of Amyloid Polypeptides hIAPP and Aβ

Roles of Apigenin and Nepetin in the Assembly Behavior and Cytotoxicity of Prion Neuropeptide PrP106-126

Transition Metal Complexes as Therapeutics: A New Frontier in Combatting Neurodegenerative Disorders through Protein Aggregation Modulation

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