Rhodanine composite fluorescence probes to detect pathological hallmarks in Alzheimer's disease models

被引:2
|
作者
Rai, Himanshu [1 ]
Singh, Rishabh [2 ]
Bharti, Prahalad Singh [2 ]
Kumar, Prabhat [3 ]
Rai, Sanskriti [2 ]
Varma, Tanmaykumar [4 ]
Chauhan, Brijesh Singh [3 ]
Nilakhe, Aishwarya Srikant [5 ]
Debnath, Joy [6 ]
Dhingra, Renu [7 ]
Mishra, Vijay N. [8 ]
Gupta, Sarika [5 ]
Krishnamurthy, Sairam [1 ]
Yang, Jian [9 ]
Garg, Prabha [4 ]
Srikrishna, Saripella [3 ]
Kumar, Saroj [2 ]
Modi, Gyan [1 ]
机构
[1] Indian Inst Technol BHU, Dept Pharmaceut Engn & Technol, Varanasi 221005, Uttar Pradesh, India
[2] All India Inst Med Sci, Dept Biophys, New Delhi 110029, India
[3] Banaras Hindu Univ, Cell & Neurobiol Lab, Dept Biochem, Inst Sci, Varanasi 221005, Uttar Pradesh, India
[4] Natl Inst Pharmaceut Educ & Res NIPER, Dept Pharmacoinformat, Sas Nagar 160062, Punjab, India
[5] Natl Inst Immunol, New Delhi 110029, India
[6] SASTRA Deemed Univ, Dept Chem, Thanjavur 613401, Tamil Nadu, India
[7] All India Inst Med Sci, Dept Anat, New Delhi 110029, India
[8] Banaras Hindu Univ, Inst Med Sci, Dept Neurol, Varanasi 221005, India
[9] Shanghai Univ, Sch Med, Shanghai 200444, Peoples R China
来源
基金
中国国家自然科学基金;
关键词
Alzheimer's disease; beta-amyloid (A beta) aggregates; Neurofibrillary tangles (NFT); Bovine serum albumin (BSA); Rhodanine dyes; Near -infrared (NIR) probes; AMYLOID-BETA; TAU FIBRILS; AGGREGATION; PLAQUES; TARGET;
D O I
10.1016/j.snb.2024.135364
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Amyloid fibrils and hyperphosphorylated tau tangles are widely acceptable histological and biochemical pathogenic markers in Alzheimer's Disease (AD). Detecting these markers at an early stage could be beneficial for differentiating AD from other neuronal anomalies. Herein, a series of rhodanine (acceptor) based dyes in conjugation with a coumarin or carbostyril (donor) were synthesized and tested their ability to detect these biomarkers. The lead probe 19 displayed staining affinity for A beta fibrils and tau tangles with little or no interaction with abundant plasma protein (BSA). Minimal cytotoxicity, brain accessibility, biocompatibility, and fluorescence sustainability across physiological pHs rendering it suitable for in -vivo imaging. Dual staining of histological samples validated affinity of probe 19 for A beta plaques and tau tangles in AD brain tissue specimens via immunofluorescence, ThT (aggregated A beta specific dye), and Tau -1 (tau filament -specific dye). Moreover, live invivo fluorescence imaging in mice and ocular labeling of A beta in AD Drosophila models extend the preclinical applicability of probe 19 for screening purposes. On behalf of the following data, we assume that probe 19 can successfully detect pathological AD biomarkers in investigational studies.
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页数:12
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