Park, Kwang-su Kim, Mi Kyoung Seo, Yujin Ha, Taewoong Yoo, Kyeongha Hyeon, Seung Jae Hwang, Yu Jin Lee, Junghee Ryu, Hoon Choo, Hyunah Chong, Youhoon 2024-01-20T00:32:11Z 2024-01-20T00:32:11Z 2021-09-03 2017-10 1948-7193 https://pubs.kist.re.kr/handle/201004/122255 Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimers disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, noninvasive imaging of tau aggregates has been highlighted as a promising diagnostic tool for AD. We have previously identified a tau-specific turn-on near-infrared fluorescent (NIRF) probe (1), and, in this study, structural modification was performed to optimize its physicochemical as well as fluorescence properties. Thus, a series of fluorescent dyes (2a-2j) composed of a variously substituted difluoroboron beta-diketonate and an N,N-dimethylaniline moiety linked by a length-extendable pi-bridge were prepared. Among those, isobutyl-substituted difluoroboron beta-ketonate with a pi-conjugated 1,4-butadienyl linker (2e) showed the most promising properties as a tau-specific NIRF probe. Compared with 1, the turn-on fluorescence of 2e was more specific to tau fibrils, and it showed 8.8- and 6.2-times higher tau-over-A beta and tau-over-BSA specificity, respectively. Also, the fluorescence intensity of 2e upon binding to tau fibrils was substantially higher (similar to 2.9 times) than that observed from 1. The mechanism for tau-specificity of 2e was investigated, which suggested that the molecular rotor-like property of 2e enables specific recognition of the microenvironment of tau aggregates to emit strong fluorescence. In transgenic cell lines stably expressing GFP-tagged tau proteins, 2e showed good colocalization with tau-GFP. Moreover, the fluorescence from 2e exhibited almost complete overlap with p-Tau antibody staining in the human AD brain tissue section. Collectively, these observations demonstrate the potential of 2e as a tau-specific fluorescent dye in both in vitro and ex vivo settings. English AMER CHEMICAL SOC ALZHEIMERS-DISEASE AMYLOID PLAQUES IMAGING PROBES NEUROFIBRILLARY PATHOLOGY SELECTIVE DETECTION MOLECULAR PROBE PET SPECTROSCOPY TANGLES CELLS A Difluoroboron beta-Diketonate Probe Shows "Turn-on" Near-Infrared Fluorescence Specific for Tau Fibrils Article 10.1021/acschemneuro.7b00224 1 ACS CHEMICAL NEUROSCIENCE, v.8, no.10, pp.2124 - 2131 ACS CHEMICAL NEUROSCIENCE 8 10 2124 2131 scie scopus 000413502700006 2-s2.0-85031676952 Biochemistry & Molecular Biology Chemistry, Medicinal Neurosciences Biochemistry & Molecular Biology Pharmacology & Pharmacy Neurosciences & Neurology Article ALZHEIMERS-DISEASE AMYLOID PLAQUES IMAGING PROBES NEUROFIBRILLARY PATHOLOGY SELECTIVE DETECTION MOLECULAR PROBE PET SPECTROSCOPY TANGLES CELLS Alzheimer&apos s disease tau-specific probe fluorescence imaging molecular rotor