识别β-淀粉样蛋白多样化聚集态的近红外荧光探针研究进展

Research progress of near-infrared fluorescent probes labeling diversified aggregation states of β-amyloid

β-淀粉样蛋白(β-amyloid,Aβ)是阿尔茨海默症(Alzheimer's disease,AD)重要病理学特征老年斑的核心组成蛋白,其在患者脑内的异常生成和聚集是AD早期诊断和确诊的重要依据之一。鉴于Aβ存在单体、寡聚体和纤维的多样化分子聚集状态,靶向识别和干预不同状态的Ap已成为精准诊断和治疗AD的重要策略。已有正电子发射断层扫描探针应用于临床检测AD患者脑内Aβ斑块,然而该类探针存在检测耗费高昂、有放射性等局限以及Aβ多样化聚集态的区分识别需求提示有必要研究新型Aβ诊断探针。本文将聚焦AD发生发展中的Aβ特征性变化,结合近红外荧光成像技术在疾病关键靶标体外检测和体内诊断中的优势,主要围绕近五年报道的可识别Aβ寡聚体和Aβ纤维的近红外荧光探针探讨不同探针识别Aβ多样化聚集态的机理,以期为新型AD精准诊断突光探针的设计和开发提供新的线索和依据。

β-amyloid(Aβ)is the core constituent protein of senile plaques,which is one of the key pathological hallmarks of Alzheimer's disease(AD).Given the existence of diversified aggregation states of Aβ including monomers,oligomers and fibers,tar­geted recognition and intervention of different Aβ states respectively has become an important strategy for precise diagnosis and treat­ment of AD.Although positron emission tomography(PET)probes have been used to detect Aβ plaques in the brain of AD patients,the limitations of its high cost and radioactivity,together with the requirement to distinguish the diversified aggregation states of Aβ suggest the necessity of development of novel Aβ diagnostic probes.Based on the advantages of near-inirared fluorescence imaging technology for in vitro detection and in vivo diagnosis of key targets,this review summarizes recently discovered near-infrared fluorescent probes labeling Aβ oligomers or Aβ fibers,and discusses the potential interaction mechanisms between probes and different Aβ aggregation states,in order to shed new light on the design and development of novel fluorescent probes for precise diagnosis of AD.