Research Paper Volume 11, Issue 17 pp 7036—7050

Enhancing the retrograde axonal transport by curcumin promotes autophagic flux in N2a/APP695swe cells

Jie Liang1,2, *, , Fanlin Zhou1,2, *, , Xiaomin Xiong1,2, , Xiong Zhang2, , Shijie Li1,2, , Xiaoju Li1,2, , Minna Gao1, , Yu Li1,2, ,

  • 1 Department of Pathology, School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
  • 2 Institute of Neuroscience, School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
* Equal contribution

Received: February 19, 2019       Accepted: August 21, 2019       Published: September 6, 2019
How to Cite

Copyright © 2019 Liang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The accumulation of autophagosomes and dysfunction at the axonal terminal of neurons play crucial roles in the genesis and development of Alzheimer’s disease (AD). Abnormalities in neuron axonal transport-related proteins prevent autophagosome maturation in AD. Curcumin, a polyphenol plant compound, has been shown to exert neuroprotective effects by increasing autophagy in AD, but the underlying mechanism of its effect on autophagy axon transport remains elusive. This study investigated the effects of curcumin on autophagosome formation and axonal transport in N2a/APP695swe cells (AD cell model) as well as the mechanism underlying those effects. Curcumin treatment significantly increased the expression of Beclin1, Atg5, and Atg16L1, induced the formation of autophagosomes, and promoted autophagosome–lysosome fusion in N2a/APP695swe cells. At the same time, curcumin promoted the expression of dynein, dynactin, and BICD2 as well as their binding to form the retrograde axonal transport molecular motor complex. Moreover, curcumin also increased the expression of the scaffolding proteins Rab7- interacting lysosomal protein (RILP) and huntingtin in N2a/APP695swe cells. Taken together, our findings indicate that curcumin increases autophagic flux by promoting interactions among autophagic axonal transport-related proteins and inducing lysosome–autophagosome fusion. This study provides evidence suggesting the potential use of curcumin as a novel treatment for AD.


AD: Alzheimer’s disease; APP: Amyloid precursor protein; Aβ: Amyloid-β; NFTs: Neurofibrillary tangles; BICD2: Bicaudal D, two-tailed D; RILP: Rab7- interacting lysosomal protein); Dynactin: Dynamic Actin; LC3: MAP1LC3B, MAP1A/1BLC3; P62: Sequestosome 1; Beclin 1: ATG6 or VPS30; Atg5: Autophagy-related gene 5; Atg16: Autophagy-related gene 16; DIC: Dynein Intermediate Chain; LAMP: Lysosomal-associated membrane protein; KIF: Kinesin family member; DHC-1: Dynein, cytoplasmic1, heavy chain1; DLC-3: Dynein, light chain, Tctex-type1; P50: Dynacin2; P150: P150Glued; EHNA: (Erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride; Baf A1: Bafilomycin A1; BCA: Bicinchoninic acid; HRP: Avidin-Horseradish Peroxidase; TEM: Transmission electron microscopy.