TY - JOUR
T1 - The Effect of Ethanol on Disassembly of Amyloid-β1-42 Pentamer Revealed by Atomic Force Microscopy and Gel Electrophoresis
AU - Matsui, Atsuya
AU - Bellier, Jean Pierre
AU - Kanai, Takeshi
AU - Satooka, Hiroki
AU - Nakanishi, Akio
AU - Terada, Tsukasa
AU - Ishibe, Takafumi
AU - Nakamura, Yoshiaki
AU - Taguchi, Hiroyasu
AU - Naruse, Nobuyasu
AU - Mera, Yutaka
N1 - Funding Information:
Funding: This work was supported by a Grant-in-Aid for Scientific Research C (19K05207) from JSPS KAKENHI, Japan.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - The most common type of dementia, Alzheimer’s disease, is associated with senile plaques formed by the filamentous aggregation of hydrophobic amyloid-β (Aβ) in the brains of patients. Small oligomeric assemblies also occur and drugs and chemical compounds that can interact with such assemblies have attracted much attention. However, these compounds need to be solubilized in appropriate solvents, such as ethanol, which may also destabilize their protein structures. As the impact of ethanol on oligomeric Aβ assembly is unknown, we investigated the effect of various concentrations of ethanol (0 to 7.2 M) on Aβ pentameric assemblies (Aβp) by combining blue native-PAGE (BN-PAGE) and ambient air atomic force microscopy (AFM). This approach was proven to be very convenient and reliable for the quantitative analysis of Aβ assembly. The Gaussian analysis of the height histogram obtained from the AFM images was correlated with band intensity on BN-PAGE for the quantitative estimation of Aβp. Our observations indicated up to 1.4 M (8.3%) of added ethanol can be used as a solvent/vehicle without quantitatively affecting Aβ pentamer stability. Higher concentration induced significant destabilization of Aβp and eventually resulted in the complete disassembly of Aβp.
AB - The most common type of dementia, Alzheimer’s disease, is associated with senile plaques formed by the filamentous aggregation of hydrophobic amyloid-β (Aβ) in the brains of patients. Small oligomeric assemblies also occur and drugs and chemical compounds that can interact with such assemblies have attracted much attention. However, these compounds need to be solubilized in appropriate solvents, such as ethanol, which may also destabilize their protein structures. As the impact of ethanol on oligomeric Aβ assembly is unknown, we investigated the effect of various concentrations of ethanol (0 to 7.2 M) on Aβ pentameric assemblies (Aβp) by combining blue native-PAGE (BN-PAGE) and ambient air atomic force microscopy (AFM). This approach was proven to be very convenient and reliable for the quantitative analysis of Aβ assembly. The Gaussian analysis of the height histogram obtained from the AFM images was correlated with band intensity on BN-PAGE for the quantitative estimation of Aβp. Our observations indicated up to 1.4 M (8.3%) of added ethanol can be used as a solvent/vehicle without quantitatively affecting Aβ pentamer stability. Higher concentration induced significant destabilization of Aβp and eventually resulted in the complete disassembly of Aβp.
KW - Amyloid-β
KW - Atomic force microscopy
KW - Gaussian fitting
KW - Gel electrophoresis
KW - Oligomer
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U2 - 10.3390/ijms23020889
DO - 10.3390/ijms23020889
M3 - Article
C2 - 35055076
AN - SCOPUS:85122781060
SN - 1422-0067
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 2
M1 - 889
ER -