Corynoxine isomers decrease levels of amyloid-β peptide and amyloid-β precursor protein by promoting autophagy and lysosome biogenesis

Siva Durairajan,Yingyu Huang,Leilei Chen,Liangfeng Liu,Min Li,Juxian Song

doi:10.1186/1750-1326-8-s1-p16

Siva Durairajan, Yingyu Huang + Show 4 more

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https://doi.org/10.1186/1750-1326-8-s1-p16

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Journal: Molecular Neurodegeneration	Publication Date: Jan 1, 2013
Citations: 6	License type: cc-by

Affiliation: Hong Kong Baptist University

Abstract

Background One of the key histopathological features of Alzheimer’s disease (AD) is the formation of neuritic plaques characterized by accumulation of amyloid b-peptide (Ab) derived from amyloid precursor protein (APP). Impairment of the autophagy-lysosomal degradation pathway has been associated with AD. Recently we have identified a novel natural autophagy inducer, corynoxine B (Cory-B), a major oxindole alkaloid from the Chinese medicinal plant Uncaria rhynchophylla (Miq.) Jacks (Gouteng in Chinese). In this study, we have also established that corynoxine (Cory) and its isomer of Cory-B, not only increases basal level of autophagy but also increases the lysosomal activity in neuronal cell lines. Interestingly Cory but not Cory-B showed the enhanced lysosomal activities.

Highlights

One of the key histopathological features of Alzheimer’s disease (AD) is the formation of neuritic plaques characterized by accumulation of amyloid b-peptide (Ab) derived from amyloid precursor protein (APP)
We found that Cory- or corynoxine B (Cory-B) mediated decreases in Ab are due to changes in its precursor protein APP, by measuring the level of full-length APP and APP-carboxy terminal fragment (CTF) in cell lysates from N2a-sSwedAPP
We found that Cory and Cory B dose-dependently increased levels of LC3-II, an autophagy specific marker in N2aSwedAPP cells

Summary

Introduction

One of the key histopathological features of Alzheimer’s disease (AD) is the formation of neuritic plaques characterized by accumulation of amyloid b-peptide (Ab) derived from amyloid precursor protein (APP). Impairment of the autophagy-lysosomal degradation pathway has been associated with AD. We have identified a novel natural autophagy inducer, corynoxine B (Cory-B), a major oxindole alkaloid from the Chinese medicinal plant Uncaria rhynchophylla (Miq.) Jacks (Gouteng in Chinese). We have established that corynoxine (Cory) and its isomer of Cory-B, increases basal level of autophagy and increases the lysosomal activity in neuronal cell lines. Cory but not Cory-B showed the enhanced lysosomal activities

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