ChemInform Abstract: Ganglioside Cluster-Mediated Aggregation and Cytotoxicity of Amyloid β-Peptide: Molecular Mechanism and Inhibition

ChemInform ◽  
2010 ◽  
Vol 41 (32) ◽  
pp. no-no
Author(s):  
Katsumi Matsuzaki
Keyword(s):  
Molecular Mechanism ◽  
Amyloid Β ◽  
Amyloid Β Peptide

Modeling Copper Binding to the Amyloid-β Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction

2012 ◽  
Vol 116 (39) ◽  
pp. 11899-11910 ◽  
Author(s):  
Sara Furlan ◽  
Christelle Hureau ◽  
Peter Faller ◽  
Giovanni La Penna
Keyword(s):  
Molecular Mechanism ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Copper Binding

scholarly journals Glucocorticoids Facilitate Astrocytic Amyloid-β Peptide Deposition by Increasing the Expression of APP and BACE1 and Decreasing the Expression of Amyloid-β-Degrading Proteases

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2704-2715 ◽  
Author(s):  
Yanyan Wang ◽  
Maoquan Li ◽  
Jun Tang ◽  
Min Song ◽  
Xueqing Xu ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Primary Cultures ◽  
Amyloid Β ◽  
The Elderly ◽  
Stress Factors ◽  
Amyloid Β Peptide ◽  
Insulin Degrading Enzyme ◽  
Basal Cortisol ◽  
Metalloproteinase 9

In most cases, the molecular mechanism underlying the pathogenesis of sporadic Alzheimer's disease (AD) is unknown. Elevated basal cortisol levels in AD patients suggest that glucocorticoids (GC) may contribute to the development and/or maintenance of AD. Amyloid plaques are the hallmark of AD, and they are considered to play an early role in the AD process. However, little is known about how their formation is regulated by stress and GC. Astrocyte accumulation is one of the earliest neuropathological changes in AD. Here, we report that GC elevated amyloid-β (Aβ) production in primary cultures of astrocytes by increasing amyloid precursor protein (APP) and β-site APP-cleaving enzyme 1 gene expression. Notably, GC administered to normal, middle-aged mice promoted the expression of APP and β-site APP-cleaving enzyme 1 in astrocytes, as determined by double immunofluorescence. Additionally, confocal microscopy and ELISA revealed that GC markedly reduced Aβ degradation and clearance by astrocytes in vitro, indicating a decreased neuroprotective capacity of the astrocytes. This may have been due to the decrease of several Aβ-degrading proteases, such as insulin-degrading enzyme and matrix metalloproteinase-9. These effects occurred through the activation of GC receptors. Taken together, our results demonstrate that GC can enhance the production of Aβ, reduce its degradation in astrocytes, and provide a molecular mechanism linking stress factors to AD. Our study suggests that GC can facilitate AD pathogenesis and that reducing GC in the elderly and early AD patients would be beneficial.

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.

Insights into amyloid disease from fly models

2014 ◽  
Vol 56 ◽  
pp. 69-83 ◽  
Author(s):  
Ko-Fan Chen ◽  
Damian C. Crowther
Keyword(s):  
Drosophila Melanogaster ◽  
Neurodegenerative Disorders ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Pathogenesis ◽  
Amyloid Aggregates ◽  
Aβ Amyloid ◽  
Polypeptide Chains ◽  
Amyloid Diseases

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.

Analytical methods to explore Amyloid-β-Peptide variants beyond Aβ1-40 and Aβ1-42

2015 ◽  
Vol 48 (06) ◽  
Author(s):  
H Esselmann ◽  
C Hafermann ◽  
O Jahn ◽  
I Kraus ◽  
J Vogelgsang ◽  
...  
Keyword(s):  
Analytical Methods ◽  
Amyloid Β ◽  
Amyloid Β Peptide

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Is it All Said for NSAIDs in Alzheimer’s Disease? Role of Mitochondrial Calcium Uptake

2018 ◽  
Vol 15 (6) ◽  
pp. 504-510 ◽  
Author(s):  
Sara Sanz-Blasco ◽  
Maria Calvo-Rodríguez ◽  
Erica Caballero ◽  
Monica Garcia-Durillo ◽  
Lucia Nunez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Amyloid Β ◽  
Epidemiological Data ◽  
Amyloid Β Peptide ◽  
Aβ Oligomers ◽  
Mitochondrial Potential ◽  
Disease Modifying Drugs ◽  
Definitive Evidence

Objectives: Epidemiological data suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Unfortunately, recent trials have failed in providing compelling evidence of neuroprotection. Discussion as to why NSAIDs effectivity is uncertain is ongoing. Possible explanations include the view that NSAIDs and other possible disease-modifying drugs should be provided before the patients develop symptoms of AD or cognitive decline. In addition, NSAID targets for neuroprotection are unclear. Both COX-dependent and independent mechanisms have been proposed, including γ-secretase that cleaves the amyloid precursor protein (APP) and yields amyloid β peptide (Aβ). Methods: We have proposed a neuroprotection mechanism for NSAIDs based on inhibition of mitochondrial Ca2+ overload. Aβ oligomers promote Ca2+ influx and mitochondrial Ca2+ overload leading to neuron cell death. Several non-specific NSAIDs including ibuprofen, sulindac, indomethacin and Rflurbiprofen depolarize mitochondria in the low µM range and prevent mitochondrial Ca2+ overload induced by Aβ oligomers and/or N-methyl-D-aspartate (NMDA). However, at larger concentrations, NSAIDs may collapse mitochondrial potential (ΔΨ) leading to cell death. Results: Accordingly, this mechanism may explain neuroprotection at low concentrations and damage at larger doses, thus providing clues on the failure of promising trials. Perhaps lower NSAID concentrations and/or alternative compounds with larger dynamic ranges should be considered for future trials to provide definitive evidence of neuroprotection against AD.

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