As amyloid β (Aβ) is at the centre of pathogenesis of Alzheimer's disease (AD), Aβ aggregate-specific probes for in vivo studies of Aβ are potentially important for the early diagnosis and the assessment of ne...As amyloid β (Aβ) is at the centre of pathogenesis of Alzheimer's disease (AD), Aβ aggregate-specific probes for in vivo studies of Aβ are potentially important for the early diagnosis and the assessment of new treatment strategies in the AD brain by noninvasive imaging. Several series of compounds derived from Congo red (CR) and Thioflavin T (ThT) have been evaluated as potential probes for the Aβ imaging. They include a diversity of core structures contributing to their affinities to Aβ. Small-molecule inhibi- tors were known to inhibit the formation of Aβ oligomers and fibrils. This inhibition has to be performed in such a way that these inhibitors bind to Aβ in the binding channel where Aβ-binding probes should sit. Therefore, several of them were used as novel core structures to develop Aβ probes, with their de- rivatives exhibiting good Aβ affinities. This approach will facilitate the design of a variety of candidates for Aβ probe molecules and anti-aggregation-therapeutic drugs. Moreover, the finding of Aβ probes with diverse core structures recognized by binding sites on Aβs will likely provide a promising per- spective for the design of 99mTc-labeled probe-derived molecules.展开更多
基金the National Natural Science Foundation of China (Grant No. 20471011)
文摘As amyloid β (Aβ) is at the centre of pathogenesis of Alzheimer's disease (AD), Aβ aggregate-specific probes for in vivo studies of Aβ are potentially important for the early diagnosis and the assessment of new treatment strategies in the AD brain by noninvasive imaging. Several series of compounds derived from Congo red (CR) and Thioflavin T (ThT) have been evaluated as potential probes for the Aβ imaging. They include a diversity of core structures contributing to their affinities to Aβ. Small-molecule inhibi- tors were known to inhibit the formation of Aβ oligomers and fibrils. This inhibition has to be performed in such a way that these inhibitors bind to Aβ in the binding channel where Aβ-binding probes should sit. Therefore, several of them were used as novel core structures to develop Aβ probes, with their de- rivatives exhibiting good Aβ affinities. This approach will facilitate the design of a variety of candidates for Aβ probe molecules and anti-aggregation-therapeutic drugs. Moreover, the finding of Aβ probes with diverse core structures recognized by binding sites on Aβs will likely provide a promising per- spective for the design of 99mTc-labeled probe-derived molecules.
