[헬스코리아뉴스 / 박민주] A new platform has been developed that helps to quickly discover compounds or bioproteins that synthesize amyloid-β (Aβ) oligomers known to cause Alzheimer’s on the surface of nanoparticles and decompose them.
The research team of Professor Dae-Sung Yoon of Korea University synthesized amyloid beta oligomer in the form of a protein corona (aggregate formed by agglomeration of proteins on the surface of nanoparticles) on the surface of nanoparticles in collaboration with Professor Jeonghoon Lee of Kwangwoon University, Professor Gyudo Lee of Korea University, and Professor Kyosun Hwang of Kyunghee University. , We developed a platform that can search (screen) compounds that selectively degrade only oligomers.
By using the developed platform, the time required to search for compounds can be shortened from several days to within a day, and it is possible to explore by using the expensive amyloid beta 50 times less than the previous one. The research team expects that this achievement will stimulate the discovery of candidates for Alzheimer’s treatment.
Currently, amyloid beta oligomer is the main cause of Alzheimer’s disease, but it is difficult to synthesize and purify pure oligomers, and because there is no fluorescent substance that can be labeled, it was difficult to search for drug candidates targeting it in large quantities.
The research team succeeded in coating only pure amyloid beta oligomer in the form of a protein corona on the surface of plasmonic nanoparticles. We developed a drug discovery platform using the principle that when the protein corona is decomposed by a candidate compound, the surface of the nanoparticles is exposed and the solution turns red when the absorbance changes due to aggregation.
① Plasmonic nanoparticles: These are metallic nanoparticles that exhibit local surface plasmon resonance.
② Localized surface plasmonic phenomenon: Optical properties that occur when metal nanoparticles and light react. Depending on the size and structure of the nanoparticles, it exhibits unique absorption properties.
It is now possible to select compounds or bioproteins that selectively decompose oligomers by changing the color of the solution without additional treatment for fluorescent materials or tracking.
The research team validated the platform using six low-molecular chemicals known to help relieve Alzheimer’s in practice and two bioproteins that remove amyloid beta in vivo.
The results of this study were published on the 27th in the international academic journal’Nature Communications’, and were carried out with support from the mid-sized research project, the original technology development project, and the 4th stage BK21 project promoted by the Ministry of Science and ICT and the Korea Research Foundation. .
(a) PNAC complex formation process.
(b, c) TEM image of the formation process.
(d) Cryo-TEM image of amyloid corona decomposition according to drug treatment.
(e) Colorimetric drug screening using PNAC.
Based on the plasmonic nanoparticles, amyloid beta (Amyloid-β, Aβ) was deposited to synthesize a plasmonic nanoparticle amyloid corona (PNAC) in the form of a protein corona.
This technology is a technology that quantitatively evaluates the efficacy of a drug (colorimetric method) by changing the color of a solution based on the phenomenon of localized surface plasmon resonance (LSPR) caused by nanoparticle aggregation.
Pictures and explanations provided by Daesung Yoon/Dongtaek Lee, Korea University
(a, b) Verification of amyloid corona composition using graphene-antibody biosensor.
(c) Analysis of surface charge and size of PNAC.
(d) component analysis of PNAC using XPS.
(e) PNAC freeze-drying test result
A graphene-antibody biosensor was used to determine the morphological characteristics of the amyloid corona present on the PNAC surface.
Through the Aβ-specific 6E10 antibody, the oligomer-specific A11 antibody, and the fibril-specific antibody OC, the morphological characteristics of the amyloid corona were verified as Aβ oligomers known as the main cause of Alzheimer’s.
In addition, it was confirmed that a uniform amyloid corona was formed on the PNAC surface through various biochemical verification methods.
Pictures and explanations provided by Daesung Yoon/Dongtaek Lee, Korea University
Aβ oligomer degradation efficacy was quantitatively analyzed using Protease XIV and Metrix metallopeptidase 9 (MMP-9), known as protein enzymes capable of degrading Aβ.
In particular, in the case of MMP-9, it was found that the decomposition activity differs markedly depending on the type of Aβ composition (Aβ(1-42) or Aβ (1-40), and the enzyme activity was at an extremely low concentration (10 fg/ml). ) Level.
Pictures and explanations provided by Daesung Yoon/Dongtaek Lee, Korea University
(ae) Changes in absorbance of PNAC by treatment with EGCG, curcumin, glutathione, rutin and tramiprosate
(f) Quantification of the decomposition effect of each drug modeled in a dose-response relationship.
(g) parameters accordingly (Hillslope, ECG50, Maximal Efficacy)
(h) Amyloid degradation efficacy of each drug expressed as Max efficacy/EC50
PNAC was used to quantitatively analyze the Aβ oligomer decomposition effect of low-molecular substances known to be helpful in Alzheimer’s treatment.
Based on the analysis results, it was verified that the drug screening platform developed by this research team can be used to discover drugs that can remove Aβ oligomers, known as the main cause of Alzheimer’s.
Pictures and explanations provided by Daesung Yoon/Dongtaek Lee, Korea University
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