[Prof. Sihyun Ham] Chemical Fluorescent Probe for Detection of Aβ Oligomers
content
The first molecular probe for selective in vivo detection of oligomeric amyloid β-peptide (Aβ) against monomeric and fully aggregated species is demonstrated by Prof. Sihyun Ham and coworkers. Structural binding model of Aβ oligomer complex with the probe offers the molecular mechanism of the Aβ oligomer selectivity.
Abstract
Aggregation of amyloid β-peptide (Aβ) is implicated in the pathology of Alzheimer’s disease (AD), with the soluble, Aβ oligomeric species thought to be the critical pathological species. Identification and characterization of intermediate species formed during the aggregation process is crucial to the understanding of the mechanisms by which oligomeric species mediate neuronal toxicity and following disease progression. Probing these species proved to be extremely challenging, as evident by the lack of reliable sensors, due to their heterogeneous and transient nature. We describe here an oligomer-specific fluorescent chemical probe, BoDipy-Oligomer (BD-Oligo), developed through the use of the diversity-oriented fluorescent library approach (DOFLA) and high-content, imaging-based screening. This probe enables dynamic oligomer monitoring during fibrillogenesis in vitro and shows in vivo Aβ oligomers staining possibility in the AD mice model.
J. Am. Chem. Soc., 2015, 137 (42), 13503~13509.