scholarly journals Ethanol Alleviates Amyloid-β-Induced Toxicity in an Alzheimer’s Disease Model of Caenorhabiditis elegans

2021 ◽  
Vol 13 ◽  
Author(s):  
Shuju Bai ◽  
Wenbo Wang ◽  
Zhiwei Zhang ◽  
Mengyao Li ◽  
Zehan Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Nuclear Translocation ◽  
Senile Plaques ◽  
Disease Model ◽  
Amyloid Β ◽  
Small Heat Shock Protein ◽  
Heat Shock Protein Genes

Amyloid-β, a hallmark of Alzheimer’s disease, forms toxic intracellular oligomers and extracellular senile plaques resulting in neuronal toxicity. Ethanol is widely consumed worldwide. Moderate ethanol consumption has numerous benefits in humans. We found that ethanol could significantly extend the lifespan of Caenorhabiditis elegans in a previous study. Based on that study, we tested the effect of ethanol on Alzheimer’s disease transgenic Caenorhabiditis elegans strain CL4176, which expresses amyloid-β1-42 peptide in body wall muscle cells. Ethanol delayed paralysis and reduced amyloid-β oligomers in Caenorhabiditis elegans worms of the CL4176 strain. Moreover, ethanol could induce the nuclear translocation of DAF-16 in the nematodes. However, in worms that were fed daf-16 RNAi bacteria, ethanol no longer delayed the paralysis. The qPCR assays showed that ethanol increases the expression of daf-16, hsf-1 and their common target genes- small heat shock protein genes. In addition, we also found that ethanol could increase lysosome mass in the CL4176 worms. In summary, our study indicated that ethanol attenuated amyloid-β toxicity in the Alzheimer’s disease model of Caenorhabiditis elegans via increasing the level of lysosomes to promote amyloid-β degradation and upregulating the levels of small heat shock protein genes to reduce amyloid-β aggregation.

scholarly journals Heat Shock Protein Inspired Nanochaperones Restore Amyloid‐β Homeostasis for Preventative Therapy of Alzheimer's Disease

2019 ◽  
Vol 6 (22) ◽  
pp. 1901844 ◽  
Author(s):  
Huiru Yang ◽  
Xinyu Li ◽  
Lin Zhu ◽  
Xiaohui Wu ◽  
Shaozhi Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Amyloid Β ◽  
Preventative Therapy

Sulforaphane Upregulates the Heat Shock Protein Co-Chaperone CHIP and Clears Amyloid-β and Tau in a Mouse Model of Alzheimer's Disease

2018 ◽  
Vol 62 (12) ◽  
pp. 1800240 ◽  
Author(s):  
Siyoung Lee ◽  
Bo-Ryoung Choi ◽  
Jisung Kim ◽  
Frank M. LaFerla ◽  
Jung Han Yoon Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heat Shock ◽  
Mouse Model ◽  
Heat Shock Protein ◽  
Amyloid Β ◽  
Model Of Alzheimer’S Disease

scholarly journals Targeted Lipidomics of Mitochondria in a Cellular Alzheimer’s Disease Model

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1062
Author(s):  
Irina Kurokin ◽  
Anna Andrea Lauer ◽  
Daniel Janitschke ◽  
Jakob Winkler ◽  
Elena Leoni Theiss ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unsaturated Fatty Acids ◽  
Senile Plaques ◽  
Disease Model ◽  
Amyloid Β ◽  
Lipid Homeostasis ◽  
Shotgun Lipidomics ◽  
App Processing ◽  
Amyloidogenic Processing

Alzheimer’s disease (AD) is neuropathologically characterized by the accumulation of Amyloid-β (Aβ) in senile plaques derived from amyloidogenic processing of a precursor protein (APP). Recently, changes in mitochondrial function have become in the focus of the disease. Whereas a link between AD and lipid-homeostasis exists, little is known about potential alterations in the lipid composition of mitochondria. Here, we investigate potential changes in the main mitochondrial phospholipid classes phosphatidylcholine, phosphatidylethanolamine and the corresponding plasmalogens and lyso-phospholipids of a cellular AD-model (SH-SY5Y APPswedish transfected cells), comparing these results with changes in cell-homogenates. Targeted shotgun-lipidomics revealed lipid alterations to be specific for mitochondria and cannot be predicted from total cell analysis. In particular, lipids containing three and four times unsaturated fatty acids (FA X:4), such as arachidonic-acid, are increased, whereas FA X:6 or X:5, such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), are decreased. Additionally, PE plasmalogens are increased in contrast to homogenates. Results were confirmed in another cellular AD model, having a lower affinity to amyloidogenic APP processing. Besides several similarities, differences in particular in PE species exist, demonstrating that differences in APP processing might lead to specific changes in lipid homeostasis in mitochondria. Importantly, the observed lipid alterations are accompanied by changes in the carnitine carrier system, also suggesting an altered mitochondrial functionality.

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

scholarly journals NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Mariana Van Zeller ◽  
Diogo M. Dias ◽  
Ana M. Sebastião ◽  
Cláudia A. Valente
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Nlrp3 Inflammasome ◽  
Neuronal Death ◽  
Inflammatory Responses ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Wide Range

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.

scholarly journals Perturbation of chromatin architecture on ecdysterone induction of Drosophila melanogaster small heat shock protein genes.

1989 ◽  
Vol 9 (1) ◽  
pp. 332-335 ◽  
Author(s):  
S E Kelly ◽  
I L Cartwright
Keyword(s):  
Drosophila Melanogaster ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Intergenic Region ◽  
Small Heat Shock Protein ◽  
Dnase I ◽  
Developmentally Regulated ◽  
Regulatory Interactions ◽  
Chromatin Architecture ◽  
Heat Shock Protein Genes

Alterations in the pattern of DNase I hypersensitivity were observed on ecdysterone-stimulated transcription of Drosophila melanogaster small heat shock protein genes. Perturbations were induced near hsp27 and hsp22, coupled with an extensive domain of chromatin unfolding in the intergenic region between hsp23 and the developmentally regulated gene 1. These regions represent candidates for ecdysterone regulatory interactions.

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