amyloid polypeptides
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2021 ◽  
Vol 14 (11) ◽  
pp. 1118
Author(s):  
Taisei Tanaka ◽  
Vipul V. Betkekar ◽  
Ken Ohmori ◽  
Keisuke Suzuki ◽  
Hideyuki Shigemori

The number of people worldwide suffering from Alzheimer’s disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates in the pancreas are considered cytotoxic and the cause of the development of AD and T2D, respectively. Thus, inhibiting amyloid polypeptide aggregation and disaggregation existing amyloid aggregates are promising approaches in the therapy and prevention against both diseases. Therefore, in this research, we evaluated the Aβ/hIAPP anti-aggregation and disaggregation activities of A-type procyanidins 1–7 and their substructures 8 and 9, by conducting structure–activity relationship studies and identified the active site. The thioflavin-T (Th-T) assay, which quantifies the degree of aggregation of amyloid polypeptides based on fluorescence intensity, and transmission electron microscopy (TEM), employed to directly observe amyloid polypeptides, were used to evaluate the activity. The results showed that catechol-containing compounds 1–6 exhibited Aβ/hIAPP anti-aggregation and disaggregation activities, while compound 7, without catechol, showed no activity. This suggests that the presence of catechol is important for both activities. Daily intake of foods containing A-type procyanidins may be effective in the prevention and treatment of both diseases.



2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Łukasz Nierzwicki ◽  
Michał Olewniczak ◽  
Paweł Chodnicki ◽  
Jacek Czub

Abstract$$\gamma$$ γ -Secretase is an enzyme known to cleave multiple substrates within their transmembrane domains, with the amyloid precursor protein of Alzheimer’s Disease among the most prominent examples. The activity of $$\gamma$$ γ -secretase strictly depends on the membrane cholesterol content, yet the mechanistic role of cholesterol in the substrate binding and cleavage remains unclear. In this work, we used all-atom molecular dynamics simulations to examine the role of cholesterol in the initial binding of a direct precursor of $$\beta$$ β -amyloid polypeptides by $$\gamma$$ γ -secretase. We showed that in cholesterol-rich membranes, both the substrate and the enzyme region proximal to the active site induce a local membrane thinning. With the free energy methods we found that in the presence of cholesterol the substrate binds favorably to the identified exosite, while cholesterol depletion completely abolishes the binding. To explain these findings, we directly examined the role of hydrophobic mismatch in the substrate binding to $$\gamma$$ γ -secretase, showing that increased membrane thickness results in higher propensity of the enzyme to bind substrates. Therefore, we propose that cholesterol promotes substrate binding to $$\gamma$$ γ -secretase by increasing the membrane thickness, which leads to the negative hydrophobic mismatch between the membrane and binding partners.



2021 ◽  
Vol 22 ◽  
pp. 100966
Author(s):  
Yi Lai ◽  
Fenglin Li ◽  
Zhifeng Zou ◽  
Madiha Saeed ◽  
Zhiai Xu ◽  
...  


Science ◽  
2021 ◽  
Vol 371 (6536) ◽  
pp. 1368-1374 ◽  
Author(s):  
Jun Lu ◽  
Yao Xue ◽  
Kalil Bernardino ◽  
Ning-Ning Zhang ◽  
Weverson R. Gomes ◽  
...  

Chiral assemblies of plasmonic nanoparticles are known for strong circular dichroism but not for high optical asymmetry, which is limited by the unfavorable combination of electrical and magnetic field components compounded by strong scattering. Here, we show that these limitations can be overcome by the long-range organization of nanoparticles in a manner similar to the liquid crystals and found in helical assemblies of gold nanorods with human islet amyloid polypeptides. A strong, polarization-dependent spectral shift and the reduced scattering of energy states with antiparallel orientation of dipoles activated in assembled helices increased optical asymmetry g-factors by a factor of more than 4600. The liquid crystal–like color variations and the nanorod-accelerated fibrillation enable drug screening in complex biological media. Improvement of long-range order can also provide structural guidance for the design of materials with high optical asymmetry.



Author(s):  
Daigo Nomoto ◽  
Tatsuhiko Tsunoda ◽  
Hideyuki Shigemori


2019 ◽  
Vol 10 (11) ◽  
pp. 4522-4534 ◽  
Author(s):  
Jufei Xu ◽  
Cong Zhao ◽  
Xiangyi Huang ◽  
Weihong Du


2019 ◽  
Vol 87 (7) ◽  
pp. 541-550 ◽  
Author(s):  
Xinyue Su ◽  
Ke Wang ◽  
Na Liu ◽  
Jiawen Chen ◽  
Yong Li ◽  
...  


2019 ◽  
Vol 14 (3) ◽  
pp. 486-496 ◽  
Author(s):  
Liang Ma ◽  
Chen Yang ◽  
Lianqi Huang ◽  
Yuchen Chen ◽  
Yang Li ◽  
...  


2019 ◽  
Vol 11 (11) ◽  
pp. 10462-10471 ◽  
Author(s):  
Ibrahim Javed ◽  
Jiacheng He ◽  
Aleksandr Kakinen ◽  
Ava Faridi ◽  
Wen Yang ◽  
...  


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