Abstract | AIMS: Axonal degeneration is a pathological symbol in the early stage of Alzheimer's disease (AD), which can be triggered by amyloid-β (Aβ) peptide deposition. Growing evidence indicates that deficit of autophagy eventually leads to the axonal degeneration. Our previous studies have shown that Dendrobium nobile Lindl alkaloid (DNLA) had protective effect on neuron impairment in vivo and in vitro; however, the underlying mechanisms is still unclear. METHODS: We exposed cultured hippocampus neurons to Aβ25-35 to investigate the effect of DNLA in vitro. Axonal degeneration was evaluated by immunofluorescence staining and MTT assay. Neurons overexpressing GFP-LC3B were used to measure the formation of autophagosome. Autophagosome-lysosome fusion, the lysosomal pH, and cathepsin activity were assessed to reflect autophagy process. Proteins of interest were analyzed by Western blot. RESULTS: DNLA pretreatment significantly inhibited axonal degeneration induced by Aβ25-35 peptide in vitro. Further studies revealed DNLA treatment increased autophagic flux through promoting formation and degradation of autophagosome in hippocampus neurons. Moreover, enhancement of autophagic flux was responsible for the protective effects of DNLA on axonal degeneration. CONCLUSIONS: DNLA prevents Aβ25-35 -induced axonal degeneration via activation of autophagy process and could be a novel therapeutic target.
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Authors | Li-Sheng Li, Yan-Liu Lu, Jing Nie, Yun-Yan Xu, Wei Zhang, Wen-Jin Yang, Qi-Hai Gong, Yuan-Fu Lu, Yang Lu, Jing-Shan Shi |
Journal | CNS neuroscience & therapeutics
(CNS Neurosci Ther)
Vol. 23
Issue 4
Pg. 329-340
(Apr 2017)
ISSN: 1755-5949 [Electronic] England |
PMID | 28261990
(Publication Type: Journal Article)
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Copyright | © 2017 John Wiley & Sons Ltd. |
Chemical References |
- Alkaloids
- Amyloid beta-Peptides
- LC3 protein, rat
- Microtubule-Associated Proteins
- Peptide Fragments
- Synaptophysin
- amyloid beta-protein (25-35)
- Green Fluorescent Proteins
- Cathepsins
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Topics |
- Alkaloids
(pharmacology)
- Amyloid beta-Peptides
(toxicity)
- Animals
- Animals, Newborn
- Apoptosis
(drug effects)
- Autophagy
(drug effects)
- Cathepsins
(metabolism)
- Cells, Cultured
- Dendrobium
(chemistry)
- Gene Expression Regulation
(drug effects)
- Green Fluorescent Proteins
(genetics, metabolism)
- Hippocampus
(cytology)
- Lysosomes
(drug effects, metabolism)
- Microtubule-Associated Proteins
(genetics, metabolism)
- Nerve Degeneration
(chemically induced)
- Neurons
(drug effects)
- Peptide Fragments
(toxicity)
- Rats
- Rats, Sprague-Dawley
- Synaptophysin
(metabolism)
- Time Factors
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