scholarly journals Investigation of the Iron Oxide Nanoparticle Effects on Amyloid Precursor Protein Processing in Hippocampal Cells

2021 ◽  
Author(s):  
Leila Sadeghi ◽  
◽  
Arezu Marefat ◽  
Keyword(s):  
Iron Oxide ◽  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Magnetic Particles ◽  
Therapeutic Potential ◽  
Precursor Protein ◽  
Neonatal Rat ◽  
Amyloid Precursor Protein Processing ◽  
Iron Oxide Nanoparticle ◽  
Dependent Manner

Introduction: Iron oxide nanoparticles (Fe2O3-NPs) are small magnetic particles that widely used in different aspects of biology and medicine in modern life. Fe2O3-NP accumulated in the living cells due to absence of active system to excrete the iron ions so damages cellular organelles by highly reactivity. Method: Herein cytotoxic effects of Fe2O3-NP with 50 nm size were investigated on primary culture of neonatal rat hippocampus by MTT assay. Pathophysiological signs of Alzheimer disease such as amyloid precursor protein (APP) expression, Aβ aggregation, soluble APPα and APPβ secretion also were investigated in hippocampal cells treated by various concentration of NP for different exposure time. Results: Our results revealed, Fe2O3-NP treatment causes oxidative stress in cells that accompanied by upregulation of the APP and Aβ in a concentration dependent manner. NP exposing also leads to more secretion of sAPPβ rather than sAPPα that concluded to increased activation of β-secretase in NP received cells. All of the harmful effects accumulate in neurons that could not be renovated so lead to neurodegeneration in Alzheimer disease. Conclusion: This study approved iron-based NPs could help to develop the Alzheimer and related neurological disorders and explained why some of the iron chelators have therapeutic potential in Alzheimer disease.

scholarly journals Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing

2008 ◽  
Vol 183 (2) ◽  
pp. 339-352 ◽  
Author(s):  
Takashi Sakurai ◽  
Kumi Kaneko ◽  
Misako Okuno ◽  
Koji Wada ◽  
Taku Kashiyama ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Amyloid Β Peptide ◽  
Dependent Manner ◽  
App Processing ◽  
Membrane Microdomain ◽  
Activity Dependent

Neuronal activity has an impact on β cleavage of amyloid precursor protein (APP) by BACE1 to generate amyloid-β peptide (Aβ). However, the molecular mechanisms underlying this effect remain to be elucidated. Cholesterol dependency of β cleavage prompted us to analyze immunoisolated APP-containing detergent-resistant membranes from rodent brains. We found syntaxin 1 as a key molecule for activity-dependent regulation of APP processing in cholesterol-dependent microdomains. In living cells, APP associates with syntaxin 1–containing microdomains through X11–Munc18, which inhibits the APP–BACE1 interaction and β cleavage via microdomain segregation. Phosphorylation of Munc18 by cdk5 causes a shift of APP to BACE1-containing microdomains. Neuronal hyperactivity, implicated in Aβ overproduction, promotes the switching of APP microdomain association as well as β cleavage in a partially cdk5-dependent manner. We propose that microdomain switching is a mechanism of cholesterol- and activity-dependent regulation of APP processing in neurons.

G-lymphatic, vascular and immune pathways for Aβ clearance cascade and therapeutic targets for Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Saurav Chakraborty ◽  
Jyothsna ThimmaReddygari ◽  
Divakar Selvaraj
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Complement System ◽  
Therapeutic Targets ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Amyloid Beta Peptide ◽  
Beta Peptide ◽  
Immune Pathways

The Alzheimer disease is a age related neurodegenerative disease. The factors causing alzheimer disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer disease progression. Among them, neuroinflammation, oxidative stress and apoptosis play a major role because of accumulation of extracellular amyloid beta peptides. Here, the clearance of amyloid beta peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines and the complement system also have a major role in Alzheimer disease. The physiological clearance pathways involved in amyloid beta peptide are glymphatic, vascular and immune pathways. Amyloid precursor protein, low density lipoprotein receptor-related protein 1, receptor for advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines and microglia are involved in amyloid beta peptide clearance pathways across the blood brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid beta agglomeration. This insoluble amyloid beta leads to neurodegenerative cascade and neuronal cell death occurs. Studies had shown disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for alzheimer disease via focussing on pathways for amyloid beta clearance are discussed.

scholarly journals Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats

2021 ◽  
Vol 22 (8) ◽  
pp. 3829
Author(s):  
Mohamed F. Dora ◽  
Nabil M. Taha ◽  
Mohamed A. Lebda ◽  
Aml E. Hashem ◽  
Mohamed S. Elfeky ◽  
...  
Keyword(s):  
Iron Oxide ◽  
B Cell Lymphoma ◽  
Basal Diet ◽  
Protective Role ◽  
Iron Oxide Nanoparticle ◽  
Albino Rats ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Brain

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

scholarly journals Amyloid Precursor Protein in Platelets of Patients With Alzheimer Disease

2001 ◽  
Vol 58 (3) ◽  
Author(s):  
Barbara Borroni ◽  
Francesca Colciaghi ◽  
Lucia Pastorino ◽  
Carla Pettenati ◽  
Elisabetta Cottini ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Precursor Protein

AMYLOID PRECURSOR PROTEIN IN SENILE PLAQUES OF ALZHEIMER DISEASE

The Lancet ◽  
1988 ◽  
Vol 332 (8613) ◽  
pp. 746 ◽  
Author(s):  
George Perry ◽  
Sandra Lipphardt ◽  
Madhu Kancherla ◽  
Pierluigi Gambetti ◽  
Linda Maggiora ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Senile Plaques ◽  
Precursor Protein
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