scholarly journals Effects of salvianolic acid A on β-amyloid mediated toxicity in Caenorhabditis elegans model of Alzheimer’s disease

2020 ◽  
Author(s):  
Chee Wah Yuen ◽  
Mardani Abdul Halim ◽  
Nazalan Najimudin ◽  
Ghows Azzam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Caenorhabditis Elegans ◽  
Senile Plaques ◽  
Amyloid Peptide ◽  
Salvianolic Acid ◽  
Aggregation Effect ◽  
Salvianolic Acid A ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

AbstractAlzheimer’s disease (AD) is a brain disease attributed to the accumulation of extracellular senile plaques comprising β-amyloid peptide (Aβ). In this study, a transgenic Caenorhabditis elegans containing the human beta amyloid Aβ42 gene which exhibited paralysis when expressed, was used to study the anti-paralysis effect of salvianolic acid A. Various concentrations ranging from 1 μg/ml to 100 μg/ml of salvianolic acid A were tested and exhibited the highest effect on the worm at the concentration of 100 μg/ml. For anti-aggregation effect, 14 μg/ml salvianolic acid A (within 4 mg/ml of Danshen) showed a significant level of inhibition of the formation of Aβ fibrils. An amount of 100 μg/ml of salvianolic acid A had the potential in reducing the ROS but did not totally obliterate the ROS production in the worms. Salvianolic acid A was found to delay the paralysis of the transgenic C. elegans, decrease Aβ42 aggregation and decreased Aβ-induced oxidative stress.

scholarly journals Tocotrienol decreases β-amyloid mediated toxicity in Caenorhabditis elegans model of Alzheimer’s disease

2020 ◽  
Author(s):  
Chee Wah Yuen ◽  
Mardani Abdul Halim ◽  
Vikneswaran Murugaiyah ◽  
Nazalan Najimudin ◽  
Ghows Azzam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Caenorhabditis Elegans ◽  
Senile Plaques ◽  
Amyloid Peptide ◽  
Model Of Alzheimer’S Disease ◽  
Aβ Aggregation ◽  
Anti Oxidant ◽  
Β Amyloid ◽  
Β Amyloid Peptide

AbstractAlzheimer’s disease (AD) is a neurological disease caused by the accumulation of extracellular senile plaques consisting of β-amyloid peptide (Aβ) in the brain. A transgenic Caenorhabditis elegans which demonstrated paralysis due to the expression of human beta amyloid Aβ42 gene was used to study the anti-paralysis effect of mixed tocotrienols. The content of the mixed tocotrienols were 12.1% α-, 2.7% β-, 18.6% γ-, and 8.1% δ-tocotrienols. Mixed tocotrienols significantly delayed the Aβ-induced paralysis in the transgenic nematode and exhibited anti-oxidant properties towards Aβ-generated oxidative stress. The mixture also presented potent inhibitory activities against Aβ aggregation with an IC50 value of 600 ng/ml. It is concluded that mixed tocotrienols could potentially serve as a new therapeutic candidate for AD.

scholarly journals AIP-1 ameliorates β-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease model

2009 ◽  
Vol 18 (15) ◽  
pp. 2739-2747 ◽  
Author(s):  
Wail M. Hassan ◽  
David A. Merin ◽  
Virginia Fonte ◽  
Christopher D. Link
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Caenorhabditis Elegans ◽  
Disease Model ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Ingredients in Zijuan Pu’er Tea Extract Alleviate β-Amyloid Peptide Toxicity in a Caenorhabditis elegans Model of Alzheimer’s Disease Likely through DAF-16

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 729 ◽  
Author(s):  
Fangzhou Du ◽  
Lin Zhou ◽  
Yan Jiao ◽  
Shuju Bai ◽  
Lu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Caenorhabditis Elegans ◽  
Protective Effect ◽  
Nuclear Translocation ◽  
Amyloid Β ◽  
Amyloid Peptide ◽  
C Elegans ◽  
Β Amyloid

Amyloid-β, one of the hallmarks of Alzheimer’s disease (AD), is toxic to neurons and can also cause brain cell death. Oxidative stress is known to play an important role in AD, and there is strong evidence that oxidative stress is associated with amyloid-β. In the present study we report the protective effect of Zijuan Pu’er tea water extract (ZTWE) and the mixture of main ingredients (+)-catechins, caffeine and procyanidin (MCCP) in ZTWE on β-amyloid-induced toxicity in transgenic Caenorhabditis elegans (C. elegans) CL4176 expressing the human Aβ1–42 gene. ZTWE, (+)-catechins, caffeine, procyanidin and MCCP delayed the β-amyloid-induced paralysis to different degrees. The MCCP treatment did not affect the transcript abundance of amyloid-β transgene (amy-1); however, Thioflavin T staining showed a significant decrease in Aβ accumulation compared to untreated worms. Further research using transgenic worms found that MCCP promoted the translocation of DAF-16 from cytoplasm to nucleus and increased the expression of superoxide dismutase 3 (SOD-3). In addition, MCCP decreased the reactive oxygen species (ROS) content and increased the SOD activity in CL4176 worms. In conclusion, the results suggested that MCCP had a significant protective effect on β-amyloid-induced toxicity in C. elegans by reducing β-amyloid aggregation and inducing DAF-16 nuclear translocation that could activate the downstream signal pathway and enhance resistance to oxidative stress.

scholarly journals The Dynamics of β-Amyloid Proteoforms Accumulation in the Brain of a 5xFAD Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 23 (1) ◽  
pp. 27
Author(s):  
Anna E. Bugrova ◽  
Polina A. Strelnikova ◽  
Maria I. Indeykina ◽  
Alexey S. Kononikhin ◽  
Natalia V. Zakharova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Senile Plaques ◽  
The Elderly ◽  
Mobility Separation ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid ◽  
Ion Mobility Separation ◽  
The Brain

Alzheimer’s disease (AD) is the leading cause of dementia among the elderly. Neuropathologically, AD is characterized by the deposition of a 39- to 42-amino acid long β-amyloid (Aβ) peptide in the form of senile plaques. Several post-translational modifications (PTMs) in the N-terminal domain have been shown to increase the aggregation and cytotoxicity of Aβ, and specific Aβ proteoforms (e.g., Aβ with isomerized D7 (isoD7-Aβ)) are abundant in the senile plaques of AD patients. Animal models are indispensable tools for the study of disease pathogenesis, as well as preclinical testing. In the presented work, the accumulation dynamics of Aβ proteoforms in the brain of one of the most widely used amyloid-based mouse models (the 5xFAD line) was monitored. Mass spectrometry (MS) approaches, based on ion mobility separation and the characteristic fragment ion formation, were applied. The results indicated a gradual increase in the Aβ fraction of isoD7-Aβ, starting from approximately 8% at 7 months to approximately 30% by 23 months of age. Other specific PTMs, in particular, pyroglutamylation, deamidation, and oxidation, as well as phosphorylation, were also monitored. The results for mice of different ages demonstrated that the accumulation of Aβ proteoforms correlate with the formation of Aβ deposits. Although the mouse model cannot be a complete analogue of the processes occurring in the human brain in AD, and several of the observed parameters differ significantly from human values supposedly due to the limited lifespan of the model animals, this dynamic study provides evidence on at least one of the possible mechanisms that can trigger amyloidosis in AD, i.e., the hypothesis on the relationship between the accumulation of isoD7-Aβ and the progression of AD-like pathology.

scholarly journals Apolipoprotein E forms stable complexes with recombinant Alzheimer's disease β-amyloid precursor protein

1997 ◽  
Vol 325 (1) ◽  
pp. 169-175 ◽  
Author(s):  
Cristina HAAS ◽  
Pilar CAZORLA ◽  
Carlos DE MIGUEL ◽  
Fernando VALDIVIESO ◽  
Jesús VÁZQUEZ
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Senile Plaques ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Reducing Conditions ◽  
Β Amyloid

Apolipoprotein E (apoE), a protein genetically linked to the incidence of Alzheimer's disease, forms SDS-stable complexes in vitro with β-amyloid peptide (Aβ), the primary component of senile plaques. In the present study, we investigated whether apoE was able to bind full-length Aβ precursor protein (APP). Using a maltose-binding-protein–APP fusion protein and human very-low-density lipoprotein (VLDL), we detected an interaction of apoE with APP that was inhibited by Aβ or anti-apoE antibody. Saturation-binding experiments indicated a single binding equilibrium with an apparent 1:1 stoichiometry and a dissociation constant of 15 nM. An interaction was also observed using apoE from cerebrospinal fluid or delipidated VLDL, as well as recombinant apoE. APP·apoE complexes were SDS-stable, and their formation was not inhibited by reducing conditions; however, they were dissociated by SDS under reducing conditions. ApoE·APP complexes formed high-molecular-mass aggregates, and competition experiments suggested that amino acids 14–23 of Aβ are responsible for complex-formation. Finally, no differences were found when studying the interaction of APP with apoE3 or apoE4. Taken together, our results demonstrate that apoE may form stable complexes with the Aβ moiety of APP with characteristics similar to those of complexes formed with isolated Aβ, and suggest the intriguing possibility that apoE–APP interactions may be pathologically relevant in vivo.

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