Open AccessDendrobium nobile Lindl alkaloid, a novel autophagy inducer, protects against axonal degeneration induced by Aβ 25‐35 in hippocampus neurons in vitro
Author(s) -
Li LiSheng,
Lu YanLiu,
Nie Jing,
Xu YunYan,
Zhang Wei,
Yang WenJin,
Gong QiHai,
Lu YuanFu,
Lu Yang,
Shi JingShan
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12678
Subject(s) - autophagy , autophagosome , microbiology and biotechnology , lysosome , western blot , degeneration (medical) , chemistry , hippocampus , biology , neuroscience , biochemistry , apoptosis , pathology , enzyme , medicine , gene
Summary 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 Aβ 25‐35 to investigate the effect of DNLA in vitro. Axonal degeneration was evaluated by immunofluorescence staining and MTT assay. Neurons overexpressing GFP ‐ LC 3B 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 Aβ 25‐35 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 Aβ 25‐35 ‐induced axonal degeneration via activation of autophagy process and could be a novel therapeutic target.