A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease

Tian

Proc. Natl. Acad. Sci. U.S.A.

et al. 2015

Self Cite

192

180

Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to monitoring therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied successfully to monitoring therapy for Alzheimer's disease (AD). Although several NIRF probes for detecting amyloid beta (Aβ) species of AD have been reported, none of these probes has been used to monitor changes of Aβs during therapy. In this article, we demonstrated that CRANAD-3, a curcumin analog, is capable of detecting both soluble and insoluble Aβ species. In vivo imaging showed that the NIRF signal of CRANAD-3 from 4-mo-old transgenic AD (APP/PS1) mice was 2.29-fold higher than that from age-matched wild-type mice, indicating that CRANAD-3 is capable of detecting early molecular pathology. To verify the feasibility of CRANAD-3 for monitoring therapy, we first used the fast Aβ-lowering drug LY2811376, a well-characterized beta-amyloid cleaving enzyme-1 inhibitor, to treat APP/PS1 mice. Imaging data suggested that CRANAD-3 could monitor the decrease in Aβs after drug treatment. To validate the imaging capacity of CRANAD-3 further, we used it to monitor the therapeutic effect of CRANAD-17, a curcumin analog for inhibition of Aβ cross-linking. The imaging data indicated that the fluorescence signal in the CRANAD-17-treated group was significantly lower than that in the control group, and the result correlated with ELISA analysis of brain extraction and Aβ plaque counting. It was the first time, to our knowledge, that NIRF was used to monitor AD therapy, and we believe that our imaging technology has the potential to have a high impact on AD drug development.Alzheimer's | amyloid | imaging | fluorescence | curcumin

Section: Resultsmentioning

confidence: 99%

“…Two-photon microscopic imaging has been an important tool for studying amyloidosis of AD (57,(72)(73)(74). However, most of the fluorescent probes have short emission, which can limit imaging depth significantly.…”

Section: Discussionmentioning

confidence: 99%

Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

Tian

Proc. Natl. Acad. Sci. U.S.A.

et al. 2015

Self Cite

192

180

“…Using a two-step red-shift strategy, Ran et al designed an decreased upon mixing with the tested Aβ species, which differs from most other reported probes [68] . Further investigation is necessary before this probe could be a theranostic agent for AD.…”

Section: Derivatives Of Stilbenementioning

confidence: 81%

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

Ren

Tang

et al. 2016

Acta Pharmacol Sin

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.

Israel Journal of Chemistry

“…This difference is essential to distinguish between the two situations, and is the basis for the imaging contrast of the technique. However, despite the large number of markers that have been proposed over the last years, the mechanisms regulating the photophysical processes undergone by the free and bound markers remain largely unknown . In this regard, computational chemistry can offer precious insight into both deactivation pathways of the markers and their binding properties towards different kinds of fibers.…”

Section: Fluorescence Imaging: Requirements For Amyloid Markersmentioning

confidence: 99%

“…In particular, in the last 20 years, several classes of organic fluorescent molecules have been designed and studied for their ability to interact specifically with amyloid deposits in the brain, and for their suitable fluorescence properties, which may be of interest for clinical applications . Among the several reviews on Alzheimer′s disease and fluorescence imaging that are available,,,, this work offers a brief overview of selected classes of organic fluorescent markers for amyloid detection.…”

Section: Introductionmentioning

confidence: 99%

Fluorescent Markers for Amyloid‐β Detection: Computational Insights

Peccati

Pantaleone

Solans‐Monfort

et al. 2016

In vivo detection of cerebral amyloid‐β plaques is essential for an early diagnosis of Alzheimer′s disease. Optical imaging, which employs fluorescent markers emitting in the near‐infrared range, is a growing alternative to nuclear techniques, with indisputable advantages. The rational design of amyloid markers requires optimization of both the optical and binding properties, and of their mutual interaction. In this work, the structural aspects that determine the performance of selected amyloid markers have been analyzed, focusing on the contributions offered by computational techniques.