Structure-Selective Anisotropy Assay for Amyloid Beta Oligomers

Matveeva, Evgenia G.; Rudolph, Alan S.; Moll, Jonathan R.; Thompson, Richard B.

doi:10.1021/cn3001262

Cited by 26 publications

(26 citation statements)

References 26 publications

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“…Ac onformationally sensitive bis-pyrene-labeled peptide (Ab [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] )w as also constructed for an oligomerspecific fluorescencea ssay. [83] Specific binding of Ab oligomers to the peptide could introduce ac hange in the fluorescence spectrumw ith ac hange of pyrene monomer fluorescence anisotropy. This simple,r apid, and anisotropy assay for Ab oligomer detectioni si mportant for understanding the role of Ab oligomers in AD and monitoring Ab oligomers in biological samples.…”

Section: Fluorescents Ensorsmentioning

confidence: 99%

Detection of Aβ Monomers and Oligomers: Early Diagnosis of Alzheimer's Disease

Zhou

Liu

Hao

et al. 2016

Chemistry An Asian Journal

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Alzheimer's disease (AD), as the most common progressive neurodegenerative disorder, is pathologically characterized by deposition of extracellular plaque composed of amyloid-β peptide (Aβ). Different assembled states of Aβ have been considered as both important biomarkers and drug targets for the diagnosis and therapy of AD. Recent studies demonstrate that small, diffusible Aβ oligomers formed by aggregation of Aβ monomers are the major toxic agents in AD. Therefore, the development of reliable assays for Aβ (both monomers and oligomers) will be important for the early differential diagnosis of dementia, predicting the progression of AD, as well as monitoring the effectiveness of novel anti-Aβ drugs for AD. In this review, we summarize the recent progress made in the development of techniques for detection of Aβ monomers and oligomers. In particular, the principles governing the design of these sensors are classified and summarized. Moreover, the advantages and disadvantages of the assays are evaluated. This review also discusses the improvements and challenges for application of these assays in the early diagnosis of AD.

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Section: Fluorescents Ensorsmentioning

confidence: 99%

Detection of Aβ Monomers and Oligomers: Early Diagnosis of Alzheimer's Disease

Zhou

Liu

Hao

et al. 2016

Chemistry An Asian Journal

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“…36 Alternatively, the organic dye-based fluorescence assays (eg, thioflavin T [ThT]) have been commonly used for monitoring the formation of Aβ aggregates in laboratory investigation. 37,38 However, most of the dyes cannot be used to discriminate Aβ oligomer from other β-sheets of Aβ aggregates, 37 thus limiting their applications for the routine test of Aβ oligomer for early diagnosis of AD.…”

Section: Introductionmentioning

confidence: 99%

A sensitive and selective electrochemical biosensor for the determination of beta-amyloid oligomer by inhibiting the peptide-triggered in situ assembly of silver nanoparticles

Xing¹,

Feng²,

Zhang³

et al. 2017

IJN

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Soluble beta-amyloid (Aβ) oligomer is believed to be the most important toxic species in the brain of Alzheimer’s disease (AD) patients. Thus, it is critical to develop a simple method for the selective detection of Aβ oligomer with low cost and high sensitivity. In this paper, we report an electrochemical method for the detection of Aβ oligomer with a peptide as the bioreceptor and silver nanoparticle (AgNP) aggregates as the redox reporters. This strategy is based on the conversion of AgNP-based colorimetric assay into electrochemical analysis. Specifically, the peptide immobilized on the electrode surface and presented in solution triggered together the in situ formation of AgNP aggregates, which produced a well-defined electrochemical signal. However, the specific binding of Aβ oligomer to the immobilized peptide prevented the in situ assembly of AgNPs. As a result, a poor electrochemical signal was observed. The detection limit of the method was found to be 6 pM. Furthermore, the amenability of this method for the analysis of Aβ oligomer in serum and artificial cerebrospinal fluid (aCSF) samples was demonstrated.

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“…Figure 2C shows the common classes of fluorophores used in FA assays for drug discovery. Long FL dyes, such as pyrenes, 42, 43 emit in the UV spectral range. Longer wavelength fluorophores (visible, red, and NIR) tend to have shorter FLs.…”

Section: Steady-state Fluorescence Anisotropymentioning

confidence: 99%

Fluorescence anisotropy (polarization): from drug screening to precision medicine

Zhang

Berezin

2015

Expert Opinion on Drug Discovery

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Introduction Fluorescence anisotropy (FA) is one of the major established methods accepted by industry and regulatory agencies for understanding the mechanisms of drug action and selecting drug candidates utilizing a high-throughput format. Areas covered This review covers the basics of FA and complementary methods, such as fluorescence lifetime anisotropy and their roles in the drug discovery process. The authors highlight the factors affecting FA readouts, fluorophore selection, and instrumentation. Furthermore, the authors describe the recent development of a successful, commercially valuable FA assay for Long QT syndrome drug toxicity to illustrate the role that FA can play in the early stages of drug discovery. Expert opinion Despite the success in drug discovery, the FA-based technique experiences competitive pressure from other homogeneous assays. That being said, FA is an established yet rapidly developing technique, recognized by academic institutions, the pharmaceutical industry, and regulatory agencies across the globe. The technical problems encountered in working with small molecules in homogeneous assays are largely solved, and new challenges come from more complex biological molecules and nanoparticles. With that, FA will remain one of the major work-horse techniques leading to precision (personalized) medicine.

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Structure-Selective Anisotropy Assay for Amyloid Beta Oligomers

Cited by 26 publications

References 26 publications

Detection of Aβ Monomers and Oligomers: Early Diagnosis of Alzheimer's Disease

Detection of Aβ Monomers and Oligomers: Early Diagnosis of Alzheimer's Disease

A sensitive and selective electrochemical biosensor for the determination of beta-amyloid oligomer by inhibiting the peptide-triggered in situ assembly of silver nanoparticles

Fluorescence anisotropy (polarization): from drug screening to precision medicine

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