scholarly journals Amyloid β-Peptide (1–42)-Induced Oxidative Stress in Alzheimer Disease: Importance in Disease Pathogenesis and Progression

2013 ◽  
Vol 19 (8) ◽  
pp. 823-835 ◽  
Author(s):  
D. Allan Butterfield ◽  
Aaron M. Swomley ◽  
Rukhsana Sultana
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Pathogenesis

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

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.

scholarly journals Identification of Novel γ-Secretase-associated Proteins in Detergent-resistant Membranes from Brain

2012 ◽  
Vol 287 (15) ◽  
pp. 11991-12005 ◽  
Author(s):  
Ji-Yeun Hur ◽  
Yasuhiro Teranishi ◽  
Takahiro Kihara ◽  
Natsuko Goto Yamamoto ◽  
Mitsuhiro Inoue ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Affinity Purification ◽  
Amyloid Β ◽  
Anion Channel ◽  
Amyloid Β Peptide ◽  
Voltage Dependent Anion Channel ◽  
App Processing ◽  
Associated Proteins ◽  
Detergent Resistant Membranes ◽  
Aβ Production

In Alzheimer disease, oligomeric amyloid β-peptide (Aβ) species lead to synapse loss and neuronal death. γ-Secretase, the transmembrane protease complex that mediates the final catalytic step that liberates Aβ from its precursor protein (APP), has a multitude of substrates, and therapeutics aimed at reducing Aβ production should ideally be specific for APP cleavage. It has been shown that APP can be processed in lipid rafts, and γ-secretase-associated proteins can affect Aβ production. Here, we use a biotinylated inhibitor for affinity purification of γ-secretase and associated proteins and mass spectrometry for identification of the purified proteins, and we identify novel γ-secretase-associated proteins in detergent-resistant membranes from brain. Furthermore, we show by small interfering RNA-mediated knockdown of gene expression that a subset of the γ-secretase-associated proteins, in particular voltage-dependent anion channel 1 (VDAC1) and contactin-associated protein 1 (CNTNAP1), reduced Aβ production (Aβ40 and Aβ42) by around 70%, whereas knockdown of presenilin 1, one of the essential γ-secretase complex components, reduced Aβ production by 50%. Importantly, these proteins had a less pronounced effect on Notch processing. We conclude that VDAC1 and CNTNAP1 associate with γ-secretase in detergent-resistant membranes and affect APP processing and suggest that molecules that interfere with this interaction could be of therapeutic use for Alzheimer disease.

scholarly journals Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease

10.1038/78682 ◽  
2000 ◽  
Vol 6 (8) ◽  
pp. 916-919 ◽  
Author(s):  
Frédérique Bard ◽  
Catherine Cannon ◽  
Robin Barbour ◽  
Rae-Lyn Burke ◽  
Dora Games ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Alzheimer Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
The Central Nervous System
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