Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer's disease

Po Ting Chen, Zih Ten Chen, Wen Chi Hou, Lung Chih Yu, Rita P Y Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Neprilysin (NEP) is the most important Aβ-degrading enzyme. Its expression level decreases with age and inversely correlated with amyloid accumulation, suggesting its correlation with the late-onset of Alzheimer's disease. Recently, many reports showed that upregulating NEP level is a promising strategy in the prevention and therapy of Alzheimer's disease. Here, we used a sensitive fluorescence-based Aβ digestion assay to screen 25 curcumin analogs for their ability to upregulate NEP activity. To our surprise, four compounds, dihydroxylated curcumin, monohydroxylated demethoxycurcumin, and mono- and di-hydroxylated bisdemethoxycurcumin, increased NEP activity, while curcumin did not. The ability of these polyhydroxycurcuminoids to upregulate NEP was further confirmed by mRNA and protein expression levels in the cell and mouse models. Finally, feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APPswe/PS1dE9 double transgenic mice upregulated NEP levels in the brain and reduced Aβ accumulation in the hippocampus and cortex. These polyhydroxycurcuminoids offer hope in the prevention of Alzheimer's disease.

Original languageEnglish
Article number29760
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jul 13 2016

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Neprilysin
Curcumin
Alzheimer Disease
Up-Regulation
Aptitude
Amyloid
Transgenic Mice
Digestion
Hippocampus
Fluorescence
Messenger RNA
Brain
Enzymes
Proteins

ASJC Scopus subject areas

  • General

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Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer's disease. / Chen, Po Ting; Chen, Zih Ten; Hou, Wen Chi; Yu, Lung Chih; Chen, Rita P Y.

In: Scientific Reports, Vol. 6, 29760, 13.07.2016.

Research output: Contribution to journalArticle

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