title: Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer's disease Drosophila models.
abstract: BACKGROUND
  Alzheimer's disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models.
  
  
  METHODS
  Neuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated.
  
  
  RESULTS
  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. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1.
  
  
  CONCLUSIONS
  Further studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Jun-Ran
authors.initials: JR
authors.lastname: Kim
authors.forename: Seong-Baek
authors.initials: SB
authors.lastname: Lee
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Jung
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea. biomodeling@snu.ac.kr.
authors.forename: Hyung-Wook
authors.initials: HW
authors.lastname: Kwon
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Ahn
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004330:Drosophila; D005123:Eye / Q000187:drug effects / Q000254:growth & development; D005260:Female; D006801:Humans; D008136:Longevity / Q000187:drug effects; D008297:Male; D010936:Plant Extracts / Q000737:chemistry; D027343:Rhizome / Q000737:chemistry*
chemical_list: D010936:Plant Extracts; D053829:Amyloid Precursor Protein Secretases; D003474:Curcumin