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An electrokinetic potential (ζ-potential) based approach was introduced to address the amyloid degradation on ZnO-nanoflower platform. The hallmark of neurodegenerative disorders like Alzheimer's disease, Parkinson's disease (PD), Creutzfeldt-Jakob Disease (CJD), Prion- associated diseases, type-II diabetes, etc. is the deposition of misfolded protein aggregates predominantly β-sheeted in structure and fibrillar morphology, known as amyloids, in the brain and different parts of the body. Agents that can degrade these amyloids can be potential candidate for the therapy of amyloidosis. Ultrasmall nanoparticles are gaining interest due to their ability to cross blood brain barrier (BBB) which is favorable for the treatment of neurodegenerative disorders. Considering the influence of Zn 2+ in the formation of Aβ aggregates instead of fibrillation, the present study was designed based on the ZnO nanoparticles (ZnO-NP) and ZnO nanoflowers (ZnO-NF) to compare the anti amyloid ability using a model huminsulin amyloid. Fluorescence study, atomic force microscopy (AFM), IR spectroscopy (FTIR) and reduction of fibril size using dynamic light scattering showed that ZnO-NF can degrade amyloids with a higher capacity than their nanoparticle counterpart. Significant reduction in magnitude of ζ-potential in ZnO-NF treated huminsulin amyloid supported the notion to come to the consensus and became the new indicator for anti-amyloidosis. The cell viability assay of ZnO-NP and ZnO-NF at a higher dose than that used for amyloid degradation using PC12 and HaCaT cell lines showed their biocompatibility in a safe manner. Thus, it can be suggested that ZnO-NF would be a better candidate for amyloid degradation compared to ZnO-NPs due to higher surface to volume ratio of the petals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A transition of amyloidogenic protein by alternative folding pathway under certain conditions leads to the formation of protease resistant amyloid fibrils, having predominantly cross β structure. These amyloids are related to various neurodegenerative diseases and clearance of such amyloids may be a therapeutic approach for amyloid-related diseases. Insulin, that can form amyloids, is widely used as a model amyloidogenic protein for the study of various amyloid related diseases. In this study, insulin amyloids were formed in vitro and the potential of Serratiopeptidase (SP), a fibrinolytic-like serine protease, towards the dissociation of insulin amyloids was explored. The dissociation of the amyloids was demonstrated using in vitro and in vivo using zebrafish model. The amyloid dissociation property was compared with a standard amyloid dissociating enzyme nattokinase (NK). SP shows better amyloid dissociation ability than NK and therefore, SP can be considered as amyloid dissociating agent with potential as a drug candidate for different amyloid related disorders., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is diagnosed with the deposition of insoluble β-amyloid (Aβ) peptides in the neuropil of the brain leading to dementia. The extracellular deposition of the fibrillar Aβ peptide on the neurons is known as senile plaques. Therefore, Aβ degradation and clearance from the human body is a promising therapeutic approach in the medication of AD. In the current study, the enzyme lumbrokinase (LK) was extracted and purified from earthworm and its activity was utilized toward Aβ 1–42 amyloids degradation in vitro alongside with an additional enzyme serratiopeptidase (SP) considering nattokinase (NK) as a standard. The output of this study revealed that preformed Aβ 1–42 amyloids was disintegrated by both LK and SP, as demonstrated from fluorescence assay using Thioflavin T dye. In addition, dynamic light scattering study revealed the lower size of the preformed fibrils Aβ 1–42 at various time intervals after incubation with the enzymes LK and SP. Furthermore, in silico approach showed high affinity thermodynamically favorable interaction of LK as well as SP toward Aβ 1–42 amyloid. Finally, the toxicity of degraded preformed Aβ 1–42 amyloid was assessed by MTT assay which showed reduced toxicity of enzyme treated Aβ 1–42 amyloid compared to only Aβ 1–42 amyloid. The findings of the present study indicated that LK and SP, not only had Aβ 1–42 amyloid degrading potential, but also could reduce the toxicity which can make them a suitable drug candidate for AD. Furthermore, the in vivo studies are needed to be executed in future. [ABSTRACT FROM AUTHOR]

Recently discovered evidences suggest that precipitation of Alzheimer's β-amyloid (Aβ) peptide and the toxicity in Alzheimer's disease (AD) are caused by abnormal interactions with neocortical metal ions, especially Zn2+, Cu2+, and Fe3+. While many studies had focused on the role of a "single" metal ion and its interaction with Aβ peptides, such studies involving "multiple" metal ions have hardly been explored. Here, to explore the nature of codeposition of different metals, two or more metal ions along with Aβ were incubated over a solid template prepared by immobilizing Aβ42 oligomers. The influence of Zn2+, Cu2+, and Fe3+ on Aβ aggregation was investigated by two approaches: co-incubation and sequential addition. Our results using ex situ AFM, ThT-induced fluorescence, and FTIR spectroscopy indicated that the co-incubation of Cu2+, Zn2+, and Fe3+ significantly altered the morphology of aggregates. A concentration dependence study with mixed metal ions suggested that Zn2+ was required at much lower concentrations than Cu2+ to yield nonfibrillar amorphous Aβ deposits. In addition, sequential addition of Zn2+ or Cu2+ on fibrillar aggregates formed by Fe3+ demonstrated that Zn2+ and Cu2+ could possibly change the conformation of the aggregates induced by Fe3+. Our findings elucidate the coexistence of multiple metal ions through their interactions with Aβ peptides or its aggregates. [ABSTRACT FROM AUTHOR]

Zinc oxide (ZnO) is a semiconductor metal oxide nanoparticle with inherent optical properties. Among the different zinc oxide nanostructures, nanoflowers have greater surface area. Utilizing this property a reagentless biosensor has been developed for the detection of beta amyloids, a hallmark of neurodegenerative diseases like Alzheimer's disease, Creutzfeldt-Jakob Syndrome, insulin dependent type II diabetes etc. The poor fluorescence quantum yield and photobleaching effect of Thioflavin T (ThT) upon binding to the model insulin amyloid beta sheets in solution can be overcome by the present engineered biosensor where ThT acts as a target as well as a reporter to detect amyloids adsorbed on a solid template based on ZnO nanoflower. ThT was adsorbed on ZnO NFs grown over nano-silver thin film coated glass slide. The in vivo imaging system was used to detect and quantify the fluorescence intensity generated from the substrates upon binding with insulin amyloid. ZnO NFs have the waveguiding property which increases the local field intensity caused by a resonance between the guided fundamental mode and evanescent field associated with high- order modes. This resonance phenomenon reinforces the excitation of the fluorophores in close proximity of the NFs thereby exhibiting enhanced fluorescence like Fabry Pero't Resonator (FPR). Considering the engineering and sensitivity, the reported nanobiosensor developed on ZnO nanoflower can be treated as faster and cost effective amyloid sensor. [ABSTRACT FROM AUTHOR]