title: Carnosine's effect on amyloid fibril formation and induced cytotoxicity of lysozyme.
abstract: Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases.
authors.affiliation: Department of Optometry, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Josephine W
authors.initials: JW
authors.lastname: Wu
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuan-Nan
authors.initials: KN
authors.lastname: Liu
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: How
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei-An
authors.initials: WA
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Lai
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Hwai-Shen
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Chaur-Jong
authors.initials: CJ
authors.lastname: Hu
authors.affiliation: Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Steven S-S
authors.initials: SS
authors.lastname: Wang
mesh_terms: D000682:Amyloid / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D001665:Binding Sites; D002336:Carnosine / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002645:Chickens; D006801:Humans; D062105:Molecular Docking Simulation; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000682:Amyloid; D030161:Avian Proteins; D002336:Carnosine; D009113:Muramidase