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

Abstract

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.

Synthesis and evaluation of benzothiazole-triazole and benzothiadiazole-triazole scaffolds as potential molecular probes for amyloid-β aggregation

“…The OH-signal was not observed in the spectrum, due to solvent exchange. 13 [1,2,5]thiadiazole-4,7-diylbis(1H-1,2,3triazole-4,1-diyl))bis(propan-1-ol) (L3) 30 . The reaction was performed under inert conditions (N 2 ).…”

“…[1][2][3][4] Thus, development of new molecular probes for the detection of protein aggregates is of great importance in order to understand the pathology of these diseases. [5][6][7][8] For example, probes that can be prepared via a modular synthetic approach to generate structures with diversity are desirable. To date, the most commonly used ligands for studying protein aggregation are thioflavin T (ThT) and Congo red (CR) (Fig.…”

Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein

“…In contrast to PET/SPECT techniques, fluorescence imaging is monitored in real time, is inexpensive, is nonradioactive and is of high-resolution when using near-infrared fluorescence (NIRF) imaging probes. As a technique, fluorescence imaging is progressively being explored for the neuroimaging of Aβ aggregates [ 94 ]. The ideal fluorescent probe will not only possess high selectivity and binding affinity, penetrate rapidly into the BBB and be cleared quickly from normal brain regions, but will also have low background fluorescence (ideal emission wavelength of greater than 650 nm) in addition to producing a significant increase in fluorescence upon binding to target proteins.…”

Multimodal Porphyrin-Based Conjugates: Synthesis and characterization for applications as amyloid ligands, photodynamic therapy agents and chiroptical materials

“…67 Today, there is a plethora of existing ligands for Aβ aggregates, most of them using fluorescence as the means for detection. 68 Optical imaging, especially imaging using near-infrared fluorescent (NIRF) probes, has been recognized as well-exploitable method for studying Aβ aggregation. The method owes its high usability to low cost, possibility for real time detection and high resolution.…”

“…69 The existing ligands for detecting amyloid β aggregates include, inter alia, Thioflavin T and its derivatives, Congo red, stilbene-type of compounds, curcuminoids and BODIPY-derivate probes. 68 Lately, a novel class of luminescent conjugated oligothiophene ligands has been developed, and proven their superiority to the other amyloid ligands in many regards, including what comes to their selectivity and sensitivity. 70-77…”