An assessment was made of beta-site amyloid precursor protein (APP) cleaving enzyme (BACE1) inhibitory, feeding, climbing activities and lifespan of the diarylalkyls curcumin (CCN), demethoxycurcumin (DCCN) and bisdemethoxycurcumin (BDCCN) identified in the rhizomes of Curcuma longa. Based on IC50 values, BDCCN (0.024 mM) was the most inhibitory constituent, followed by DCCN (0.31 mM) and CCN (0.59 mM). Overall the three curcuminoids were significantly less inhibitory than BACE1 inhibitor IV isophthalamide (8.5 × 10-5 mM). The expression of human APP and BACE1 in compound eye of Drosophila melangaster presented rough abnormal ommatidial lattice. Co-expression of APP and BACE1 within the developing nervous system of drosophila showed climbing defects. These transgenic flies kept on media containing 1 mM of CCN and BDCCN were observed to ameliorate eye degeneration, significantly suppress locomotive dysfunctions, and increase media life time, as well as isophthalamide. CCN and BDCCN as human BACE1 inhibitory constituents may be used as potential therapeutics or lead molecules to develop Alzheimer's disease treatment drugs.

• Young-Joon Ahn(WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University)
• Hyung-Wook Kwon(WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University)
• Young-Joon Kim(Department of Life Science, Gwangju Insititute of Science and Technology)
• Seong-Back Lee(WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University)
• Jun-Ran Kim(WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University)
• Xue Wang(Entomology Major, Department of Agriculture Biotechnology, Seoul National University)