Alzheimer’s disease (AD) is the most common type of presenile and senile dementia. Human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production. We assessed anti-BACE-1 and behavioral activities of curcuminoids from Curcuma longa, curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD fly models. Neuro-protective ability of curcuminoids was assessed using fly model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. BDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC50, which was 20 and 13 times lower than those of CCN and DMCCN respectively. Expression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Supplementing diet with either 1 mM BDMCCN or CCN rescued APP/BACE1 expressing flies and kept them from developing both morphological and behavioral defects. Structural characteristics and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1.

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