title: Dendrobium nobile Lindl alkaloid, a novel autophagy inducer, protects against axonal degeneration induced by Aβ25-35in hippocampus neurons in vitro.
abstract: OBJECTIVE
  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 Aβ25-35to 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 Aβ25-35peptide 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.
authors.affiliation: Department of Chemistry, Basic Medical Faculty, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Li-Sheng
authors.identifier: http://orcid.org/0000-0001-8696-4641
authors.initials: LS
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Yan-Liu
authors.initials: YL
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Yun-Yan
authors.initials: YY
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Qi-Hai
authors.initials: QH
authors.lastname: Gong
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Department of Chemistry, Basic Medical Faculty, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Key Lab of Basic Pharmacology of Education Ministry, Zunyi Medical University, Zunyi, Guizhou, China.
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Shi
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002403:Cathepsins / Q000378:metabolism; D002478:Cells, Cultured; D031667:Dendrobium / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000470:Alkaloids; D016229:Amyloid beta-Peptides; D002403:Cathepsins; D049452:Green Fluorescent Proteins; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D016708:Synaptophysin; C526109:Anxa3 protein, rat; C074636:amyloid beta-protein (25-35)
keywords: Alzheimer's disease; Dendrobium nobile Lindl alkaloid; amyloid-β; autophagy; axonal degeneration