A spiropyran-based fluorescent probe for the specific detection of β-amyloid peptide oligomers in Alzheimer's disease

2016 ◽  
Vol 52 (57) ◽  
pp. 8865-8868 ◽  
Author(s):  
Guanglei Lv ◽  
Anyang Sun ◽  
Peng Wei ◽  
Ning Zhang ◽  
Haichuang Lan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fluorescent Probe ◽  
Amyloid Peptide ◽  
Specific Detection ◽  
Aβ Oligomers ◽  
Β Amyloid ◽  
Β Amyloid Peptide

A fluorescent probe for the specific detection of Aβ oligomers in Alzheimer's disease both in vitro and in vivo was developed.

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.

Pentapeptide Amides Interfere with the Aggregation of β-Amyloid Peptide of Alzheimer's Disease

2002 ◽  
Vol 292 (4) ◽  
pp. 931-936 ◽  
Author(s):  
Csaba Hetényi ◽  
Zoltán Szabó ◽  
Éva Klement ◽  
Zsolt Datki ◽  
Tamás Körtvélyesi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease

2005 ◽  
Vol 171 (1) ◽  
pp. 87-98 ◽  
Author(s):  
W. Haung Yu ◽  
Ana Maria Cuervo ◽  
Asok Kumar ◽  
Corrinne M. Peterhoff ◽  
Stephen D. Schmidt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Mammalian Target Of Rapamycin ◽  
Amyloid Peptide ◽  
Survival Pathways ◽  
Secretase Activity ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.

scholarly journals The inhibition of cellular toxicity of amyloid-β by dissociated transthyretin

2020 ◽  
Vol 295 (41) ◽  
pp. 14015-14024 ◽  
Author(s):  
Qin Cao ◽  
Daniel H. Anderson ◽  
Wilson Y. Liang ◽  
Joshua Chou ◽  
Lorena Saelices
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Effect ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Aβ Oligomers ◽  
Cellular Toxicity ◽  
Computational Docking

The protective effect of transthyretin (TTR) on cellular toxicity of β-amyloid (Aβ) has been previously reported. TTR is a tetrameric carrier of thyroxine in blood and cerebrospinal fluid, the pathogenic aggregation of which causes systemic amyloidosis. However, studies have documented a protective effect of TTR against cellular toxicity of pathogenic Aβ, a protein associated with Alzheimer's disease. TTR binds Aβ, alters its aggregation, and inhibits its toxicity both in vitro and in vivo. In this study, we investigate whether the amyloidogenic ability of TTR and its antiamyloid inhibitory effect are associated. Using protein aggregation and cytotoxicity assays, we found that the dissociation of the TTR tetramer, required for its amyloid pathogenesis, is also necessary to prevent cellular toxicity from Aβ oligomers. These findings suggest that the Aβ-binding site of TTR may be hidden in its tetrameric form. Aided by computational docking and peptide screening, we identified a TTR segment that is capable of altering Aβ aggregation and toxicity, mimicking TTR cellular protection. EM, immune detection analysis, and assessment of aggregation and cytotoxicity revealed that the TTR segment inhibits Aβ oligomer formation and also promotes the formation of nontoxic, nonamyloid amorphous aggregates, which are more sensitive to protease digestion. Finally, this segment also inhibits seeding of Aβ catalyzed by Aβ fibrils extracted from the brain of an Alzheimer's patient. Together, these findings suggest that mimicking the inhibitory effect of TTR with peptide-based therapeutics represents an additional avenue to explore for the treatment of Alzheimer's disease.

Strength training or green tea prevent memory deficits in a β-amyloid peptide-mediated Alzheimer's disease model

2021 ◽  
Vol 143 ◽  
pp. 111186
Author(s):  
Helen L. Schimidt ◽  
Guilherme S. Carrazoni ◽  
Alexandre Garcia ◽  
Ivan Izquierdo ◽  
Pâmela B. Mello-Carpes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Strength Training ◽  
Green Tea ◽  
Disease Model ◽  
Memory Deficits ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

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

β-Amyloid Peptide: the Cell Compartment Multi-faceted Interaction in Alzheimer’s Disease

2019 ◽  
Vol 37 (2) ◽  
pp. 250-263 ◽  
Author(s):  
Pasquale Picone ◽  
Domenico Nuzzo ◽  
Daniela Giacomazza ◽  
Marta Di Carlo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Peptide ◽  
Cell Compartment ◽  
Β Amyloid ◽  
Β Amyloid Peptide
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