scholarly journals Capturing Amyloid-β Oligomers by Stirring with Microscaled Iron Oxide Stir Bars into Magnetic Plaques to Reduce Cytotoxicity toward Neuronal Cells

Nanomaterials ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1284
Author(s):  
Yuan-Chung Tsai ◽  
Jing-Chian Luo ◽  
Te-I Liu ◽  
I-Lin Lu ◽  
Ming-Yin Shen ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Neuronal Cells ◽  
Amyloid Β ◽  
Specific Protein ◽  
M1 Polarization ◽  
Magnetic Stirring ◽  
Novel Strategy ◽  
Plaque Clearance ◽  
Ad Therapy ◽  
Phagocytic Uptake

Soluble amyloid-β oligomers (oAβ42)-induced neuronal death and inflammation response has been recognized as one of the major causes of Alzheimer’s disease (AD). In this work, a novel strategy adopting silica-coated iron oxide stir bar (MSB)-based AD therapy system via magnetic stirring-induced capture of oAβ42 into magnetic plaques (mpAβ42) and activation of microglia on cellular plaque clearance was developed. With oAβ42 being effectively converted into mpAβ42, the neurotoxicity toward neuronal cells was thus greatly reduced. In addition to the good preservation of neurite outgrowth through the diminished uptake of oAβ42, neurons treated with oAβ42 under magnetic stirring also exhibited comparable neuron-specific protein expression to those in the absence of oAβ42. The phagocytic uptake of mpAβ42 by microglia was enhanced significantly as compared to the counterpart of oAβ42, and the M1 polarization of microglia often occurring after the uptake of oAβ42 restricted to an appreciable extent. As a result, the inflammation induced by pro-inflammatory cytokines was greatly alleviated.

Fluorine-mediated synthesis of anisotropic iron oxide nanostructures for efficient T2-weighted magnetic resonance imaging

Nanoscale ◽  
2021 ◽  
Author(s):  
Tao Sun ◽  
Yiding Liu ◽  
Chunyu Zhou ◽  
Liang Zhang ◽  
Xun Kang ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Iron Oxide ◽  
Controlled Synthesis ◽  
Resonance Imaging ◽  
Fluoride Ions ◽  
Oxide Nanostructures ◽  
Weighted Magnetic Resonance Imaging ◽  
Shape Controlled ◽  
Novel Strategy ◽  
Iron Oxide Nanostructures

Herein, we developed a novel strategy for the shape-controlled synthesis of fluorine-doped iron oxide nanostructures with superior r2 values through the introduction of fluoride ions as a morphology controlling agent...

scholarly journals Photo-excited Toluidine Blue disaggregates the Repeat Tau and modulates cytoskeletal structure in neuronal cells

2020 ◽  
Author(s):  
Tushar Dubey ◽  
Nalini Vijay Gorantla ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Toluidine Blue ◽  
Neuronal Cells ◽  
Red Light ◽  
Microtubule Polymerization ◽  
Toxic Concentration ◽  
Significant Toxicity ◽  
Neuro2a Cells ◽  
High Concentrations ◽  
Novel Strategy ◽  
20 Nm

AbstractAlzheimer’s disease is a progressive neurological disorder characterized by the intracellular accumulation of Tau protein aggregates. Inhibition of protein aggregation by photo-excited dyes is emerging as novel strategy for the treatment of certain diseases. Toluidine Blue is a basic phenothiazine dye having potency of photo-excitation by irradiation with red light at 630±20 nm. In present work, we studied the effect of Toluidine Blue and photo-excited TB on aggregation of repeat Tau in-vitro using Thioflavin S fluorescence assay, SDS-PAGE and electron microscopy. Results show that TB efficiently inhabited the formation of higher order aggregates. Moreover, the photo-excited TB led to disaggregation of the mature repeat Tau fibrils. Further, studies on the effect of Toluidine blue on cell viability and cytoskeleton network of Neuro2acells show that TB was not toxic to neuronal cells at lower concentrations but at high concentrations (> 5 μM) both TB and photo-excited TB induced significant toxicity. Immunofluorescence studies on the cytoskeleton of Neuro2a cells show that Toluidine Blue and photo-excited Toluidine Blue treatment at non-toxic concentration of 0.5 μM stimulated formation of actin rich lamellipodia and filopodia structures. Tubulin networks were also differentially modulated after the treatment of Toluidine Blue and photo-excited Toluidine Blue. End Binding protein 1 (EB1) levels were observed to increase after Toluidine Blue and photo-excited Toluidine Blue treatment indicating the accelerated microtubule polymerization. The overall study suggested that Toluidine Blue inhibited the aggregation of soluble Tau and photo-excited Toluidine Blue disaggregated the pre-formed Tau filaments.

Dendrimer modified magnetic iron oxide nanoparticle/DNA/PEI ternary magnetoplexes: a novel strategy for magnetofection

2011 ◽  
Vol 21 (35) ◽  
pp. 13306 ◽  
Author(s):  
Wen-Ming Liu ◽  
Ya-Nan Xue ◽  
Na Peng ◽  
Wen-Tao He ◽  
Ren-Xi Zhuo ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticle ◽  
Magnetic Iron Oxide ◽  
Oxide Nanoparticle ◽  
Novel Strategy

Sequence analysis of MAP2 function in living cells

1994 ◽  
Vol 107 (11) ◽  
pp. 3115-3125 ◽  
Author(s):  
J. Ferralli ◽  
T. Doll ◽  
A. Matus
Keyword(s):  
Neuronal Cells ◽  
Specific Protein ◽  
Direct Result ◽  
Microtubule Binding ◽  
Amino Terminal ◽  
Rich Domain ◽  
Weak Binding ◽  
Repeat Domain ◽  
Combined Action ◽  
Process Outgrowth

Microtubule-associated protein 2 (MAP2) is an abundant neuron-specific protein that binds to microtubules through a domain near its carboxyl terminus that contains either three or four similar repeats of a 31 amino acid motif. When expressed in non-neuronal cells by transfection MAP2 stabilises microtubules and induces their rearrangement into long bundles that are capable of supporting process outgrowth. To investigate which elements in the MAP2 sequence are involved in these functions we have constructed a series of deletion mutants of the short embryonic form of MAP2, MAP2c, and transfected them into non-neuronal cells. This showed that the strength of binding to microtubules increased with the number of repeats present in the construct. However, the repeat domain itself was insufficient for microtubule binding, which required in addition contiguous sequences either amino-terminal or carboxyl-terminal to the repeats themselves. Particularly on the amino-terminal side of the repeats, where there is a proline-rich domain, step-wise increases in the length of neighbouring sequence produced a gradual increase in microtubule binding. The apparent strength of binding to microtubules produced by mutant MAP2 forms was further correlated with the degree of bundling they induced as well as with the ability of the resulting microtubules to support process outgrowth. These results indicate that the interaction of MAP2 with microtubules is mediated by the combined action of several weak binding sites, including each of the repeat motifs and elements in the sequences on either side of them, whose additive effect produces the strong binding of the native MAP2 molecule. The results further indicate that both the bundling and stiffening of microtubules by MAP2 are correlated with the strength of its binding to them and suggest that these properties are a direct result of microtubule stabilisation.

Amyloid Beta42 (Aβ42) Peptide Functionalized Iron Oxide Nanoparticles for Specific Targeting of SH-SY5Y Neuroblastoma Cells

2021 ◽  
Vol 21 (10) ◽  
pp. 5044-5050
Author(s):  
Yang Xia ◽  
Parasuraman Padmanabhan ◽  
Vimalan Vijayaragavan ◽  
Vadakke Matham Murukeshan ◽  
Balázs Gulyás
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Cellular Uptake ◽  
Neuronal Cells ◽  
Neuroblastoma Cells ◽  
Oxide Nanoparticles ◽  
Ageing Population ◽  
Amyloid Peptides ◽  
Hct 116 Cells ◽  
Aβ42 Peptide

One of the most severe diseases threatening the ageing population is Alzheimer’s disease (AD). Recent studies found that the cellular uptake of extracellular amyloid beta (Aβ) peptides can lead to a build-up of intracellular Aβ in certain neuronal cells, which consequently lead to the onset of AD pathogenesis. It is therefore hypothesized that the detection of cells that are involved in such Aβ uptake could facilitate the early diagnosis of AD. In this work, a magnetofluorescent nanoprobe was prepared conjugating dye-labeled Aβ42 peptides with iron oxide nanoparticles (IONPs). When incubated with SH-SY5Y cells, the cellular uptake of Aβ42-IONPs was enhanced, compared to that of bare IONPs. Further, by labelling SH-SY5Y and HCT-116 cells, it was found that the Aβ42-IONPs are selectively targeting the neuronal cells. This enhanced and specific neuronal targeting is attributed to the cellular uptake of extracellular amyloid by SH-SY5Y cells. In addition, the MR relaxivities of the Aβ42-IONPs are preserved after the peptides functionalization. The results suggest that the Aβ42 functionalized magnetofluorescent IONPs can be used as a bimodal probe to interrogate the cellular uptake of amyloid peptides.

Prions and Neurodegenerative Diseases: A Focus on Alzheimer’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Alessio Crestini ◽  
Francesca Santilli ◽  
Stefano Martellucci ◽  
Elena Carbone ◽  
Maurizio Sorice ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Amyloid Β ◽  
Specific Protein ◽  
Cellular Prion Protein ◽  
Aβ Oligomers ◽  
The Central Nervous System ◽  
Induced Signal

Specific protein misfolding and aggregation are mechanisms underlying various neurodegenerative diseases such as prion disease and Alzheimer’s disease (AD). The misfolded proteins are involved in prions, amyloid-β (Aβ), tau, and α-synuclein disorders; they share common structural, biological, and biochemical characteristics, as well as similar mechanisms of aggregation and self-propagation. Pathological features of AD include the appearance of plaques consisting of deposition of protein Aβ and neurofibrillary tangles formed by the hyperphosphorylated tau protein. Although it is not clear how protein aggregation leads to AD, we are learning that the cellular prion protein (PrPC) plays an important role in the pathogenesis of AD. Herein, we first examined the pathogenesis of prion and AD with a focus on the contribution of PrPC to the development of AD. We analyzed the mechanisms that lead to the formation of a high affinity bond between Aβ oligomers (AβOs) and PrPC. Also, we studied the role of PrPC as an AβO receptor that initiates an AβO-induced signal cascade involving mGluR5, Fyn, Pyk2, and eEF2K linking Aβ and tau pathologies, resulting in the death of neurons in the central nervous system. Finally, we have described how the PrPC-AβOs interaction can be used as a new potential therapeutic target for the treatment of PrPC-dependent AD.

scholarly journals Self-assembly of iron oxide precursor micelles driven by magnetic stirring time in sol–gel coatings

RSC Advances ◽  
2019 ◽  
Vol 9 (31) ◽  
pp. 17571-17580 ◽  
Author(s):  
J. López-Sánchez ◽  
A. Serrano ◽  
A. del Campo ◽  
M. Abuín ◽  
E. Salas-Colera ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Self Assembly ◽  
Sol Gel ◽  
Oxide Precursor ◽  
Magnetic Stirring ◽  
Stirring Time ◽  
Self Assembled ◽  
Sol Gel Synthesis

Sol–gel synthesis of self-assembled iron oxide precursor micelles.

Xylocoside G Reduces Amyloid-β Induced Neurotoxicity by Inhibiting NF-κB Signaling Pathway in Neuronal Cells

2012 ◽  
Vol 30 (2) ◽  
pp. 263-275 ◽  
Author(s):  
Yan Yu ◽  
Liang Zhou ◽  
Miao Sun ◽  
Ting Zhou ◽  
Kaiyin Zhong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neuronal Cells ◽  
Amyloid Β

Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present)

2019 ◽  
Vol 26 (30) ◽  
pp. 5684-5710 ◽  
Author(s):  
Ning Wang ◽  
Panpan Qiu ◽  
Wei Cui ◽  
Xiaojun Yan ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Chemical Structures ◽  
Target Drug ◽  
Single Target ◽  
Approved Drugs ◽  
Multiple Drugs ◽  
Fda Approved Drugs ◽  
Ad Therapy

: Since the last century, when scientists proposed the lock-and-key model, the discovery of drugs has focused on the development of drugs acting on single target. However, single-target drug therapies are not effective to complex diseases with multi-factorial pathogenesis. Moreover, the combination of single-target drugs readily causes drug resistance and side effects. In recent years, multi-target drugs have increasingly been represented among FDA-approved drugs. Alzheimer’s Disease (AD) is a complex and multi-factorial disease for which the precise molecular mechanisms are still not fully understood. In recent years, rational multi-target drug design methods, which combine the pharmacophores of multiple drugs, have been increasingly applied in the development of anti-AD drugs. In this review, we give a brief description of the pathogenesis of AD and provide detailed discussions about the recent development of chemical structures of anti-AD agents (2013 up to present) that have multiple targets, such as amyloid-β peptide, Tau protein, cholinesterases, monoamine oxidase, β-site amyloid-precursor protein-cleaving enzyme 1, free radicals, metal ions (Fe2+, Cu2+, Zn2+) and so on. In this paper, we also added some novel targets or possible pathogenesis which have been reported in recent years for AD therapy. We hope that these findings may provide new perspectives for the pharmacological treatment of AD.

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