Nicotine lowers the secretion of the Alzheimer's amyloid β-protein precursor that contains amyloid β-peptide in rat

2002 ◽  
Vol 4 (5) ◽  
pp. 405-415 ◽  
Author(s):  
Tadanobu Utsuki ◽  
Mohammed Shoaib ◽  
Harold W. Holloway ◽  
Donald K. Ingram ◽  
William C. Wallace ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein

scholarly journals A High-Throughput Screen to Identify Inhibitors of Amyloid β-Protein Precursor Processing

2005 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Pancham Bakshi ◽  
Yung-Feng Liao ◽  
Jun Gao ◽  
Jake Ni ◽  
Ross Stein ◽  
...  
Keyword(s):  
High Throughput ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Β Protein ◽  
High Throughput Screen ◽  
Transcription Activator ◽  
Protein Precursor ◽  
App Processing ◽  
Chemical Structures ◽  
Β Protein

Cerebral accumulation of the amyloid β-peptide (Aβ) is believed to play a key role in the pathogenesis of Alzheimer’s disease (AD). Because Aβ is produced from the proteolysis of amyloid β-protein precursor (APP) by β-and γ-secretases, these enzymes are considered important drug targets for AD. The authors have developed a luciferase-based reporter system that can identify new molecules that inhibit APP processing in a high-throughput manner. Such molecules can help in understanding the biology of APP and APP processing and in developing new drug prototypes for AD. In this system, APP is fused on its C-terminus with Gal4-VP16, a chimeric yeast-viral transcription activator, and luciferase is under control of the yeast Gal4 promoter. Compounds that modulate the luciferase signal may affect the secretases directly, interact with modifiers of these proteases, or interact with APP directly. The authors successfully interfaced this assay with a high-throughput screen, testing ~60,000 compounds with diverse chemical structures. In principle, this sensitive, specific, and quantitative assay may be useful for identifying both inhibitors and stimulators of APP processing.( Journal of Biomolecular Screening 2005:1-12)

Transcranial Laser Therapy Attenuates Amyloid-β Peptide Neuropathology in Amyloid-β Protein Precursor Transgenic Mice

2011 ◽  
Vol 23 (3) ◽  
pp. 521-535 ◽  
Author(s):  
Luis De Taboada ◽  
Jin Yu ◽  
Salim El-Amouri ◽  
Sebastiano Gattoni-Celli ◽  
Steve Richieri ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Laser Therapy ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein

Novel mutations introduced at the β-site of amyloid β protein precursor enhance the production of amyloid β peptide by BACE1 in vitro and in cells

2005 ◽  
Vol 7 (2) ◽  
pp. 139-148 ◽  
Author(s):  
Xiao-Ping Shi ◽  
Katherine Tugusheva ◽  
James E. Bruce ◽  
Adam Lucka ◽  
Elizabeth Chen-Dodson ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Β Protein ◽  
Novel Mutations ◽  
Protein Precursor ◽  
Β Protein ◽  
In Cells

scholarly journals Small Molecule Amyloid-β Protein Precursor Processing Modulators Lower Amyloid-β Peptide Levels via cKit Signaling

2019 ◽  
Vol 67 (3) ◽  
pp. 1089-1106 ◽  
Author(s):  
Ci-Di Chen ◽  
Ella Zeldich ◽  
Christina Khodr ◽  
Kaddy Camara ◽  
Tze Yu Tung ◽  
...  
Keyword(s):  
Small Molecule ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Precursor Processing ◽  
Β Protein

Mutations in the Amyloid-β Protein Precursor Reduce Mitochondrial Function and Alter Gene Expression Independent of 42-Residue Amyloid-β Peptide

2021 ◽  
pp. 1-11
Author(s):  
Chad A. Pope ◽  
Heather M. Wilkins ◽  
Russell H. Swerdlow ◽  
Michael S. Wolfe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Function ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Β Protein ◽  
Human Neuroblastoma ◽  
Altered Expression ◽  
Protein Precursor ◽  
Β Protein

Background: Dominant missense mutations in the amyloid-β protein precursor (AβPP) cause early-onset familial Alzheimer’s disease (FAD) and are associated with changes in the production or properties of the amyloid-β peptide (Aβ), particularly of the 42-residue variant (Aβ 42) that deposits in the Alzheimer’s disease (AD) brain. Recent findings, however, show that FAD mutations in AβPP also lead to increased production of longer Aβ variants of 45–49 residues in length. Objective: We aimed to test neurotoxicity of Aβ 42 vis-á-vis longer variants, focusing specifically on mitochondrial function, as dysfunctional mitochondria are implicated in the pathogenesis of AD. Methods: We generated SH-SY5Y human neuroblastoma cells stably expressing AβPP mutations that lead to increased production of long Aβ peptides with or without Aβ 42. These AβPP-expressing cells were tested for oxygen consumption rates (OCR) under different conditions designed to interrogate mitochondrial function. These cell lines were also examined for expression of genes important for mitochondrial or neuronal structure and function. Results: The mutant AβPP-expressing cells showed decreased basal OCRs as well as decreased OCRs associated with mitochondrial ATP production, even more so in the absence of Aβ 42 production. Moreover, mutant AβPP-expressing cells producing longer forms of Aβ displayed altered expression of certain mitochondrial- and neuronal-associated genes, whether or not Aβ 42 was produced. Conclusion: These findings suggest that mutant AβPP can cause mitochondrial dysfunction that is associated with long Aβ but not with Aβ 42.

scholarly journals Amyloid-β Oligomers Induce Only Mild Changes to Inhibitory Bouton Dynamics

2021 ◽  
Vol 5 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Marvin Ruiter ◽  
Christine Lützkendorf ◽  
Jian Liang ◽  
Corette J. Wierenga
Keyword(s):  
Hippocampal Slices ◽  
Inhibitory Neuron ◽  
Amyloid Β ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein ◽  
Plaque Load ◽  
Early Alzheimer’S Disease

The amyloid-β protein precursor is highly expressed in a subset of inhibitory neuron in the hippocampus, and inhibitory neurons have been suggested to play an important role in early Alzheimer’s disease plaque load. Here we investigated bouton dynamics in axons of hippocampal interneurons in two independent amyloidosis models. Short-term (24 h) amyloid-β (Aβ)-oligomer application to organotypic hippocampal slices slightly increased inhibitory bouton dynamics, but bouton density and dynamics were unchanged in hippocampus slices of young-adult AppNL - F - G-mice, in which Aβ levels are chronically elevated. These results indicate that loss or defective adaptation of inhibitory synapses are not a major contribution to Aβ-induced hyperexcitability.

scholarly journals Phosphorylation of KLC1 modifies interaction with JIP1 and abolishes the enhanced fast velocity of APP transport by kinesin-1

2017 ◽  
Vol 28 (26) ◽  
pp. 3857-3869 ◽  
Author(s):  
Kyoko Chiba ◽  
Ko-yi Chien ◽  
Yuriko Sobu ◽  
Saori Hata ◽  
Shun Kato ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Amyloid Β ◽  
Tetratricopeptide Repeat ◽  
Amyloid Β Protein ◽  
The Novel ◽  
Anterograde Transport ◽  
Interacting Protein ◽  
Protein Precursor ◽  
Kinesin Light Chain ◽  
Β Protein

In neurons, amyloid β-protein precursor (APP) is transported by binding to kinesin-1, mediated by JNK-interacting protein 1b (JIP1b), which generates the enhanced fast velocity (EFV) and efficient high frequency (EHF) of APP anterograde transport. Previously, we showed that EFV requires conventional interaction between the JIP1b C-terminal region and the kinesin light chain 1 (KLC1) tetratricopeptide repeat, whereas EHF requires a novel interaction between the central region of JIP1b and the coiled-coil domain of KLC1. We found that phosphorylatable Thr466 of KLC1 regulates the conventional interaction with JIP1b. Substitution of Glu for Thr466 abolished this interaction and EFV, but did not impair the novel interaction responsible for EHF. Phosphorylation of KLC1 at Thr466 increased in aged brains, and JIP1 binding to kinesin-1 decreased, suggesting that APP transport is impaired by aging. We conclude that phosphorylation of KLC1 at Thr466 regulates the velocity of transport of APP by kinesin-1 by modulating its interaction with JIP1b.

The upstream stimulatory factor functionally interacts with the Alzheimer amyloid β-protein precursor gene

1995 ◽  
Vol 4 (9) ◽  
pp. 1527-1533 ◽  
Author(s):  
Dora M. Kovacs ◽  
Wilma Wasco ◽  
Johanna Witherby ◽  
Kevin M. Felsenstein ◽  
Franck Brunei ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Upstream Stimulatory Factor ◽  
Protein Precursor ◽  
Β Protein ◽  
Stimulatory Factor
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