scholarly journals Conformational Characterization of Native and L17A/F19A-Substituted Dutch-Type β-Amyloid Peptides

2020 ◽  
Vol 21 (7) ◽  
pp. 2571 ◽  
Author(s):  
Kai-Cyuan He ◽  
Yi-Ru Chen ◽  
Chu-Ting Liang ◽  
Shi-Jie Huang ◽  
Chung-Ying Tzeng ◽  
...  
Keyword(s):  
Sodium Dodecyl ◽  
Amyloid Peptide ◽  
Genetic Mutations ◽  
Wild Type ◽  
Amyloid Peptides ◽  
Aβ Aggregation ◽  
Nuclear Magnetic Spectroscopy ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Some mutations which occur in the α/β-discordant region (resides 15 to 23) of β-amyloid peptide (Aβ) lead to familial Alzheimer’s disease (FAD). In vitro studies have shown that these genetic mutations could accelerate Aβ aggregation. We recently showed that mutations in this region could alter the structural propensity, resulting in a different aggregative propensity of Aβ. Whether these genetic mutations display similar effects remains largely unknown. Here, we characterized the structural propensity and aggregation kinetics of Dutch-type Aβ40 (Aβ40(E22Q)) and its L17A/F19A-substituted mutant (Aβ40(L17A/F19A/E22Q)) using circular dichroism spectroscopy, nuclear magnetic spectroscopy, and thioflavin T fluorescence assay. In comparison with wild-type Aβ40, we found that Dutch-type mutation, unlike Artic-type mutation (E22G), does not reduce the α-helical propensity of the α/β-discordant region in sodium dodecyl sulfate micellar solution. Moreover, we found that Aβ40(L17A/F19A/E22Q) displays a higher α-helical propensity of the α/β-discordant region and a slower aggregation rate than Aβ40(E22Q), suggesting that the inhibition of aggregation might be via increasing the α-helical propensity of the α/β-discordant region, similar to that observed in wild-type and Artic-type Aβ40. Taken together, Dutch-type and Artic-type mutations adopt different mechanisms to promote Aβ aggregation, however, the L17A/F19A mutation could increase the α-helical propensities of both Dutch-type and Artic-type Aβ40 and inhibit their aggregation.

scholarly journals Mechanism of Cellular Formation and In Vivo Seeding Effects of Hexameric β-amyloid Assemblies

2021 ◽  
Author(s):  
Céline Vrancx ◽  
Devkee M Vadukul ◽  
Nuria Suelves ◽  
Sabrina Contino ◽  
Ludovic D'Auria ◽  
...  
Keyword(s):  
Senile Plaques ◽  
Amyloid Peptide ◽  
Secretase Activity ◽  
Aβ Aggregation ◽  
Cellular Context ◽  
Β Amyloid ◽  
Β Amyloid Peptide ◽  
Aβ Generation

Abstract The β-amyloid peptide (Aβ) is the main constituent of senile plaques, a typical hallmark of Alzheimer’s disease (AD). Monomeric Aβ is generated through sequential processing of the amyloid precursor protein (APP), with a final step involving γ-secretase activity. In AD, Aβ monomers assemble in oligomers and ultimately fibrils depositing in plaques. Importantly, Aβ toxicity appears related to its soluble oligomeric intermediates. In particular, recombinant Aβ studies described Aβ hexamers as critical oligomeric nuclei. We recently identified hexameric Aβ assemblies in a cellular model, and revealed their ability to enhance recombinant Aβ aggregation in vitro. Here, we assessed the contribution of similar hexameric-like Aβ assemblies to the development of amyloid pathology. We report their early presence in both transgenic mice brains exhibiting human Aβ pathology and cerebrospinal fluid of AD patients, suggesting hexameric Aβ as a putative novel AD biomarker. Using isolated cell-derived hexameric Aβ, we report the potential of these assemblies to seed other human Aβ species, resulting in neuronal toxicity in vitro and amyloid deposition aggravation in vivo. In order to identify key contributors to their formation in a cellular context, we investigated the role of presenilin-1 (PS1) and presenilin-2 (PS2) in the formation of hexameric-like Aβ assemblies. As catalytic subunits of the γ-secretase complex, PS1 and PS2 can differentially participate in Aβ generation. Using CRISPR-Cas9-modified neuronal-like cell lines knockdown for each of the two presenilins, we present experimental evidence suggesting a direct link between the PS2-dependent pathway and the release of hexameric-like Aβ assemblies in extracellular vesicles.

In vitro aggregation facilitates β-amyloid peptide-(25–35)-induced amnesia in the rat

1997 ◽  
Vol 319 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Stéphanie Delobette ◽  
Alain Privat ◽  
Tangui Maurice
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Modulation of β-amyloid aggregation by graphene quantum dots

2019 ◽  
Vol 6 (6) ◽  
pp. 190271 ◽  
Author(s):  
Changliang Liu ◽  
Huan Huang ◽  
Lilusi Ma ◽  
Xiaocui Fang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Structural Changes ◽  
Graphene Quantum Dots ◽  
Amyloid Peptide ◽  
Therapeutic Drug ◽  
Amyloid Aggregation ◽  
Β Amyloid ◽  
Regulatory Effects ◽  
Β Amyloid Peptide

Misfolding and abnormal aggregation of β-amyloid peptide is associated with the onset and progress of Alzheimer's disease (AD). Therefore, modulating β-amyloid aggregation is critical for the treatment of AD. Herein, we studied the regulatory effects and mechanism of graphene quantum dots (GQDs) on 1–42 β-amyloid (Aβ 1–42 ) aggregation. GQDs displayed significant regulatory effects on the aggregation of Aβ 1–42 peptide as detected by thioflavin T (ThT) assay. Then, the changes of confirmations and structures induced by GQDs on the Aβ 1–42 aggregation were monitored by circular dichroism (CD), dynamic light scattering (DLS) and transmission electron microscope (TEM). The in vitro cytotoxicity experiments further demonstrated the feasibility of GQDs on the regulation of Aβ 1–42 aggregation. Meanwhile, the structural changes of a Aβ 1–42 /GQDs mixture in different pH revealed that electrostatic interaction was the major driving force in the co-assembly process of Aβ 1–42 and GQDs. The proposed mechanism of the regulatory effects of GQDs on the Aβ 1–42 aggregation was also deduced reasonably. This work not only demonstrated the potential feasibility of GQDs as therapeutic drug for AD but also clarified the regulatory mechanism of GQDs on the Aβ 1–42 aggregation.

scholarly journals Paper-Based Detection Device for Alzheimer’s Disease—Detecting β-amyloid Peptides (1–42) in Human Plasma

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 272
Author(s):  
Wei-Hsuan Sung ◽  
Jung-Tung Hung ◽  
Yu-Jen Lu ◽  
Chao-Min Cheng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Operating Time ◽  
Amyloid Peptide ◽  
Buffer System ◽  
Amyloid Peptides ◽  
Β Amyloid ◽  
Β Amyloid Peptide ◽  
Short Operating Time ◽  
Tremendous Impact

The diagnosis of Alzheimer’s disease (AD) is frequently missed or delayed in clinical practice. To remedy this situation, we developed a screening, paper-based (P-ELISA) platform to detect β-amyloid peptide 1–42 (Aβ42) and provide rapid results using a small volume, easily accessible plasma sample instead of cerebrospinal fluid. The protocol outlined herein only requires 3 μL of sample per well and a short operating time (i.e., only 90 min). The detection limit of Aβ42 is 63.04 pg/mL in a buffer system. This P-ELISA-based approach can be used for early, preclinical stage AD screening, including screening for amnestic mild cognitive impairment (MCI) due to AD. It may also be used for treatment and stage monitoring purposes. The implementation of this approach may provide tremendous impact for an afflicted population and may well prompt additional and expanded efforts in both academic and commercial communities.

scholarly journals Assessment of the Bioactivity of Antibodies against β-Amyloid Peptide in vitro and in vivo

2004 ◽  
Vol 1 (4-5) ◽  
pp. 160-167 ◽  
Author(s):  
M. Hasan Mohajeri ◽  
Meret N.M. Gaugler ◽  
Julia Martinez ◽  
Jay Tracy ◽  
Hong Li ◽  
...  
Keyword(s):  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Magnetic Resonance Studies of β-Amyloid Peptides

2003 ◽  
Vol 56 (5) ◽  
pp. 349 ◽  
Author(s):  
Tong-Lay Lau ◽  
Kevin J. Barnham ◽  
Cyril C. Curtain ◽  
Colin L. Masters ◽  
Frances Separovic
Keyword(s):  
Conformational Changes ◽  
Senile Plaques ◽  
Amyloid Peptide ◽  
Nmr Studies ◽  
Paramagnetic Resonance ◽  
Amyloid Peptides ◽  
Β Amyloid ◽  
Β Amyloid Peptide ◽  
Main Component ◽  
The Relationship

The deposition of senile plaques is a characteristic event in the progression of Alzheimer's disease (AD). Associated with the progression of the disease, the main component of the deposited material, the β-amyloid peptide (Aβ), undergoes a structural transition and a toxic gain of function. For this reason, extensive structural studies of Aβ and Aβ fragments have been carried out in order to determine the relationship between neurotoxicity and conformational changes of the peptide that lead to fibril formation. NMR studies in aqueous solution and in membrane-mimicking environments are reviewed, and include the effects of temperature, pH, and metal ions on Aβ structure. In addition, electron paramagnetic resonance (EPR) studies of Aβ in model membranes and the effect of metals of Aβ are discussed and demonstrate the pleiomorphic nature of the peptide. The contradictory results obtained from the various experiments are a result of studying different fragments of Aβ and illustrate the importance of studying the full-length peptide.

Alzheimerʼs β-amyloid peptide is conformationally modified by apolipoprotein E in vitro

Neuroreport ◽  
1996 ◽  
Vol 7 (3) ◽  
pp. 721-725 ◽  
Author(s):  
Claudio Soto ◽  
Adam Golabek ◽  
Thomas Wisniewski ◽  
Eduardo M. Castaño
Keyword(s):  
Apolipoprotein E ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide
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