Li Kaibo, Wang Yuxuan, Li Yanping, Shi Wenjing, Yan Jinwu
MOE International Joint Research Laboratory on Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, PR China.
School of Medicine, Foshan University, Foshan, 528225, PR China.
Talanta. 2024 Sep 1;277:126362. doi: 10.1016/j.talanta.2024.126362. Epub 2024 Jun 4.
Alzheimer's disease (AD), gradually recognized as an untreatable neurodegenerative disorder, has been considered to be closely associated with Aβ plaques, which consist of β-amyloid protein (Aβ) and is one of the crucial pathological features of AD. There are no obvious symptoms in the initial phase of AD, and thus the therapeutic interventions are important for early diagnosis of AD. Moreover, recent researches have indicated that lipid droplets might serve as a potential ancillary biomarker, and its viscosity changes are closely associated to the pathological process of AD. Herein, two newly fluorescent probes 5QSZ and BQSZ have been developed and synthesized for identifying Aβ aggregates and detecting the viscosity of lipid droplet. After selectively binding to Aβ aggregates, 5QSZ and BQSZ exhibited linear and obvious fluorescence enhancements (32.58 and 36.70 folds), moderate affinity (K = 268.0 and 148.6 nM) and low detection limits (30.11 and 65.37 nM) in aqueous solutions. Further fluorescence staining of 5QSZ on brain tissue sections of APP/PS1 transgenic mouse exhibited the higher selectivity of 5QSZ towards Aβ aggregates locating at the core of the plaques. Furthermore, 5QSZ and BQSZ displayed strong linear fluorescence emission enhancements towards viscosity changes and would be utilized to monitor variation in cellular viscosity induced by LPS or monensin. These two probes were non-cytotoxic and showed good localization in lipid droplets. Therefore, 5QSZ and BQSZ could serve as potential bi-functional fluorescent probes to image Aβ aggregates and monitor the viscosity of lipid droplets, which have significant implications for the early diagnosis and progression of AD.
阿尔茨海默病（AD）逐渐被认为是一种无法治愈的神经退行性疾病，一直被认为与Aβ斑块密切相关，Aβ斑块由β-淀粉样蛋白（Aβ）组成，是AD的关键病理特征之一。AD在初始阶段没有明显症状，因此治疗干预对于AD的早期诊断很重要。此外，最近的研究表明，脂滴可能作为一种潜在的辅助生物标志物，其粘度变化与AD的病理过程密切相关。在此，已开发并合成了两种新型荧光探针5QSZ和BQSZ，用于识别Aβ聚集体和检测脂滴的粘度。在选择性地与Aβ聚集体结合后，5QSZ和BQSZ在水溶液中表现出线性且明显的荧光增强（分别为32.58倍和36.70倍）、适度的亲和力（K = 268.0和148.6 nM）以及低检测限（30.11和65.37 nM）。5QSZ对APP/PS1转基因小鼠脑组织切片的进一步荧光染色显示，5QSZ对位于斑块核心的Aβ聚集体具有更高的选择性。此外，5QSZ和BQSZ对粘度变化表现出强烈的线性荧光发射增强，可用于监测由脂多糖或莫能菌素诱导的细胞粘度变化。这两种探针无细胞毒性，在脂滴中显示出良好的定位。因此，5QSZ和BQSZ可作为潜在的双功能荧光探针，用于对Aβ聚集体进行成像并监测脂滴的粘度，这对AD的早期诊断和病情进展具有重要意义。
