A Sensitive Aβ Oligomerization Assay for Identification of Small Molecule Inhibitors

摘要: Amyloid deposits found in Alzheimer's disease result from aggregation of  peptide which leads to loss synaptic function, chronic microglial activation and cognitive impairment. Because this, identification small mole- cule inhibitors as potential therapeutics is a topic current interest. The majority inhibitor screening approaches rely on vitro assays that lack the necessary sensitivity distinguish low-molecular weight oligomers larger, more advanced-stage fibrillar structures. Differentiating between these two structures vital concern since recent studies indicate small, early-stage are most neurotoxic form aggregate. To address this limitation, we have explored adaptability recently described ELISA-based assay for discovery oligomerization. Results show highly sensitive it able quantify oli- gomers with little 80 nM input peptide. In addition, data were obtained re-confirming function curcumin potent (IC50 = 2 μM) defining its inhibitor:peptide functional stoichiometry. Further ex- amination other known anti-aggregation compounds showed discriminate early-stage, later-stage, high-molecular These findings in- dicate new capable identifying novel molecule during initial stages assembly.