Aromatic-interaction-mediated inhibition of β-amyloid assembly structures and cytotoxicity

2017 ◽  
Vol 23 (9) ◽  
pp. 679-684 ◽  
Author(s):  
Hanyi Xie ◽  
Jiaxi Peng ◽  
Changliang Liu ◽  
Xiaocui Fang ◽  
Hongyang Duan ◽  
...  
Keyword(s):  
Β Amyloid ◽  
Amyloid Assembly ◽  
Aromatic Interaction

Fucoxanthin Inhibits β-Amyloid Assembly and Attenuates β-Amyloid Oligomer-Induced Cognitive Impairments

2017 ◽  
Vol 65 (20) ◽  
pp. 4092-4102 ◽  
Author(s):  
Siying Xiang ◽  
Fufeng Liu ◽  
Jiajia Lin ◽  
Huixin Chen ◽  
Chunhui Huang ◽  
...  
Keyword(s):  
Cognitive Impairments ◽  
Β Amyloid ◽  
Amyloid Assembly ◽  
Amyloid Oligomer

scholarly journals Protection against β-amyloid-induced synaptic and memory impairments via altering β-amyloid assembly by bis(heptyl)-cognitin

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Lan Chang ◽  
Wei Cui ◽  
Yong Yang ◽  
Shujun Xu ◽  
Wenhua Zhou ◽  
...  
Keyword(s):  
Memory Impairments ◽  
Β Amyloid ◽  
Amyloid Assembly

scholarly journals NMR-based site-resolved profiling of β-amyloid misfolding reveals structural transitions from pathologically relevant spherical oligomer to fibril

2019 ◽  
Vol 295 (2) ◽  
pp. 458-467 ◽  
Author(s):  
Yiling Xiao ◽  
Isamu Matsuda ◽  
Masafumi Inoue ◽  
Tomoya Sasahara ◽  
Minako Hoshi ◽  
...  
Keyword(s):  
Chemical Shifts ◽  
Structural Transitions ◽  
Limited Information ◽  
Distance Measurements ◽  
Tem Analysis ◽  
Negative Stain ◽  
Large Conformational Change ◽  
Β Amyloid ◽  
Amyloid Assembly ◽  
Β Sheet

Increasing evidence highlights the central role of neurotoxic oligomers of the 42-residue-long β-amyloid (Aβ42) in Alzheimer's disease (AD). However, very limited information is available on the structural transition from oligomer to fibril, particularly for pathologically relevant amyloids. To the best of our knowledge, we present here the first site-specific structural characterization of Aβ42 misfolding, from toxic oligomeric assembly yielding a similar conformation to an AD-associated Aβ42 oligomer, into a fibril. Transmission EM (TEM) analysis revealed that a spherical amyloid assembly (SPA) of Aβ42 with a 15.6 ± 2.1-nm diameter forms in a ∼30-μm Aβ42 solution after a ∼10-h incubation at 4 °C, followed by a slow conversion into fibril at ∼180 h. Immunological analysis suggested that the SPA has a surface structure similar to that of amylospheroid (ASPD), a patient-derived toxic Aβ oligomer, which had a diameter of 10–15 nm in negative-stain TEM. Solid-state NMR analyses indicated that the SPA structure involves a β-loop-β motif, which significantly differed from the triple-β motif observed for the Aβ42 fibril. The comparison of the 13C chemical shifts of SPA with those of the fibril prepared in the above conditions and interstrand distance measurements suggested a large conformational change involving rearrangements of intermolecular β-sheet into in-register parallel β-sheet during the misfolding. A comparison of the SPA and ASPD 13C chemical shifts indicated that SPA is structurally similar to the ASPD relevant to AD. These observations provide insights into the architecture and key structural transitions of amyloid oligomers relevant for AD pathology.

An usnic acid derivative as new tweezer for non-covalent aromatic interaction complex

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
B Legouin ◽  
M Chollet-Krugler ◽  
S Tomasi ◽  
P Uriac ◽  
P van de Weghe
Keyword(s):  
Acid Derivative ◽  
Usnic Acid ◽  
Aromatic Interaction

β-Amyloid secretion by human monocytes

2005 ◽  
Vol 38 (05) ◽  
Author(s):  
JM Maler ◽  
P Spitzer ◽  
M Herrmann ◽  
H Esselmann ◽  
P Lewczuk ◽  
...  
Keyword(s):  
Human Monocytes ◽  
Β Amyloid

Amentoflavone: A Bifunctional Metal Chelator that Controls the Formation of Neurotoxic Soluble Aβ42 Oligomers

2020 ◽  
Author(s):  
Liang Sun ◽  
Anuj K. Sharma ◽  
Byung-Hee Han ◽  
Liviu M. Mirica
Keyword(s):  
Reactive Oxygen Species ◽  
Metal Ions ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
Amyloid Plaques ◽  
Transition Metal Ions ◽  
Oxygen Species ◽  
High Affinity ◽  
Amyloid Aβ ◽  
Β Amyloid

<p>Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet the cause and progression of this disorder are not completely understood. While the main hallmark of AD is the deposition of amyloid plaques consisting of the β-amyloid (Aβ) peptide, transition metal ions are also known to play a significant role in disease pathology by expediting the formation of neurotoxic soluble β-amyloid (Aβ) oligomers, reactive oxygen species (ROS), and oxidative stress. Thus, bifunctional metal chelators that can control these deleterious properties are highly desirable. Herein, we show that amentoflavone (AMF) – a natural biflavonoid compound, exhibits good metal-chelating properties, especially for chelating Cu<sup>2+</sup> with very high affinity (pCu<sub>7.4</sub> = 10.44). In addition, AMF binds to Aβ fibrils with a high affinity (<i>K<sub>i</sub></i> = 287 ± 20 nM) – as revealed by a competition thioflavin T (ThT) assay, and specifically labels the amyloid plaques <i>ex vivo</i> in the brain sections of transgenic AD mice – as confirmed via immunostaining with an Ab antibody. The effect of AMF on Aβ<sub>42</sub> aggregation and disaggregation of Aβ<sub>42</sub> fibrils was also investigated, to reveal that AMF can control the formation of neurotoxic soluble Aβ<sub>42</sub> oligomers, both in absence and presence of metal ions, and as confirmed via cell toxicity studies. Furthermore, an ascorbate consumption assay shows that AMF exhibits potent antioxidant properties and can chelate Cu<sup>2+</sup> and significantly diminish the Cu<sup>2+</sup>-ascorbate redox cycling and reactive oxygen species (ROS) formation. Overall, these studies strongly suggest that AMF acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity, can also bind Cu<sup>2+</sup> and mediate its deleterious redox properties, and thus AMF has the potential to be a lead compound for further therapeutic agent development for AD. </p>

Аnticholinesterase and antioxidant activity of new binary conjugates of (с)-carbolines

2019 ◽  
Vol 484 (1) ◽  
pp. 104-108
Author(s):  
G. F. Makhaeva ◽  
E. F. Shevtsova ◽  
N. P. Boltneva ◽  
N. V. Kovaleva ◽  
E. V. Rudakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Anticholinesterase Activity ◽  
Amyloid Aggregation ◽  
Varying Length ◽  
Β Amyloid ◽  
New Compounds

This study presents the synthesis of binary tetrohydro-γ-carbolines with ditriazol spacers of varying length, which exhibit anticholinesterase and antioxidant activity, as compared to the original Dimebon prototype. Anticholinesterase activity suggests the potential ability of the new compounds to block β-amyloid aggregation induced by anticholinesterase, making them promising candidates for further research preparations for the treatment of Alzheimer's disease. Particular attention should be paid to the conjugate with an intertriazol hexamethylene spacer, which can be regarded as the leading compound in this series.

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