title: rBTI reduced β-amyloid-induced toxicity by promoting autophagy-lysosomal degradation via DAF-16 in Caenorhabditis elegans.
abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which β-amyloid (Aβ) induced toxicity was suggested as a main cause. Some substances with prolongevity effects have been shown to be protective against AD. In a previous study we demonstrated that a recombinant buckwheat trypsin inhibitor (rBTI) could prolonge the lifespan in Caenorhabditis elegans (C. elegans). Here, we investigated whether rBTI may benefit to mitigate the AD symptom by feeding the AD model C. elegans CL4176. CL4176 is a transgenic C. elegans expressing human Aβ3-42in muscle tissue. The results showed that rBTI not only could extend lifespan but also could reduce Aβ toxicity-triggered body paralysis in AD worms. Further study found the accumulation of Aβ was decreased and autophagy-lysosomal degradation pathway was activated in AD worms treated with rBTI. Moreover, the inhibition of autophagy reduced rBTI-mediated paralysis delay. Genetic analyses showed rBTI increased the transcriptional activity of dauer formation abnormal-16 (DAF-16) and the disruption of daf-16 abolished rBTI-mediated protective effect in AD worms. Taken together, these data indicated that rBTI promoted the autophagy-lysosomal degradation pathway to reduce the Aβ-induced toxicity via DAF-16 in an AD model C. elegans, implying that BTI has the potential to protect against AD.
authors.affiliation: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cui
authors.affiliation: College of Life Science, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Life Science, Shanxi University, Taiyuan 030006, PR China. Electronic address: zhwang@sxu.edu.cn.
authors.forename: Zhuanhua
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D019612:Fagopyrum / Q000737:chemistry*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010243:Paralysis / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D014361:Trypsin Inhibitors / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014361:Trypsin Inhibitors; C108831:daf-16 protein, C elegans
keywords: Alzheimer's disease; Autophagy; DAF-16; rBTI; β-Amyloid