Development of fluorescent probes that bind and stain amyloid plaques in Alzheimer’s disease

Jung, Seung-Jin; Park, Seung-Hwan; Lee, Eun Je; Park, Jeong Hoon; Kong, Young Bae; Rho, Jong Kook; Hur, Min Goo; Yang, Seung Dae; Park, Yong Dae

doi:10.1007/s12272-015-0617-4

Cited by 19 publications

(12 citation statements)

References 18 publications

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“…The solutions were incubated for 10 min at 37°C, and then their fluorescence intensity was determined at 408 nm (excitation wavelength). K D was determined as described previously [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

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A Pyridazine-Based Fluorescent Probe Targeting AβPlaques in Alzheimer’s Disease

Park

Kim

Lee

et al. 2018

Journal of Analytical Methods in Chemistry

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Accumulation of β-amyloid (Aβ) plaques comprising Aβ40 and Aβ42 in the brain is the most significant factor in the pathogenesis of Alzheimer's disease (AD). Thus, the detection of Aβ plaques has increasingly attracted interest in the context of AD diagnosis. In the present study, a fluorescent pyridazine-based dye that can detect and image Aβ plaques was designed and synthesized, and its optical properties in the presence of Aβ aggregates were evaluated. An approximately 34-fold increase in emission intensity was exhibited by the fluorescent probe after binding with Aβ aggregates, for which it showed high affinity (KD = 0.35 µM). Moreover, the reasonable hydrophobic properties of the probe (log P = 2.94) allow it to penetrate the blood brain barrier (BBB). In addition, the pyridazine-based probe was used in the histological costaining of transgenic mouse (APP/PS1) brain sections to validate the selective binding of the probe to Aβ plaques. The results suggest that the pyridazine-based compound has the potential to serve as a fluorescent probe for the diagnosis of AD.

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Section: Methodsmentioning

confidence: 99%

“…An optical data study was performed using a Maestro 2.0 in vivo imaging system. The images were acquired as described previously [ 25 ]. Solutions of probe 3 (1 μ M) were prepared with and without 20 μ M A β aggregates in PBS.…”

Section: Methodsmentioning

confidence: 99%

A Pyridazine-Based Fluorescent Probe Targeting AβPlaques in Alzheimer’s Disease

Park

Kim

Lee

et al. 2018

Journal of Analytical Methods in Chemistry

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“…Although some of these probes were developed for in vivo use, many are also applicable to fixed tissue sections. In addition, conversion of positron emission tomography (PET) probes to fluorescent probes for imaging is possible (Jung et al, 2015), suggesting that these probes use common interaction modes with amyloids that can be exploited for further development. Chemical structures and essential data for these probes can be found in Table S3.…”

Section: Nissl Body Probesmentioning

confidence: 99%

Chemical Probes for Visualizing Intact Animal and Human Brain Tissue

Lai

Gentleman

et al. 2017

Cell Chemical Biology

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Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain.

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“…13 was confirmed to penetrate the BBB and to clearly stain Aβ plaques in 14-month-old APP/PS1 mice when compared with normal controls. However, the emission wavelength of 13 after binding to Aβ aggregates is 532 nm, thus it is still not qualified for in vivo experimentation [62] .…”

Section: Derivatives Of Stilbenementioning

confidence: 99%

Advances in development of fluorescent probes for detecting amyloid-β aggregates

Ren

Tang

et al. 2016

Acta Pharmacol Sin

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With accumulating evidence suggesting that amyloid-β (Aβ) deposition is a good diagnostic biomarker for Alzheimer's disease (AD), the discovery of active Aβ probes has become an active area of research. Among the existing imaging methods, optical imaging targeting Aβ aggregates (fibrils or oligomers), especially using near-infrared (NIR) fluorescent probes, is increasingly recognized as a promising approach for the early diagnosis of AD due to its real time detection, low cost, lack of radioactive exposure and high-resolution. In the past decade, a variety of fluorescent probes have been developed and tested for efficiency in vitro, and several probes have shown efficacy in AD transgenic mice. This review classifies these representative probes based on their chemical structures and functional modes (dominant solvent-dependent mode and a novel solvent-independent mode). Moreover, the pharmaceutical characteristics of these representative probes are summarized and discussed. This review provides important perspectives for the future development of novel NIR Aβ diagnostic probes.

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Development of fluorescent probes that bind and stain amyloid plaques in Alzheimer’s disease

Cited by 19 publications

References 18 publications

A Pyridazine-Based Fluorescent Probe Targeting AβPlaques in Alzheimer’s Disease

A Pyridazine-Based Fluorescent Probe Targeting AβPlaques in Alzheimer’s Disease

Chemical Probes for Visualizing Intact Animal and Human Brain Tissue

Advances in development of fluorescent probes for detecting amyloid-β aggregates

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