Polysaccharide extracts from algae as therapeutic strategies targeting oxidative stress for polyQ-mediated SCA

• Main Authors: Jyun-Ru Jian, 簡均如
• Other Authors: Guey-Jen Lee-Chen
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/89862798804538134165

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 102 === Most age-related neurodegenerative diseases are characterized by accumulation of aberrant protein aggregates/inclusions in the affected brain regions. Several lines of evidence suggest that increased oxidative stress may involve in the pathogenesis of neurodegenerative diseases. Studies have shown that polysaccharides from several algal species have antioxidant activity. This study investigated the antioxidant activities of polysaccharide extracts from brown seaweed (fucoidan, a sulfated polysaccharide), Nostoc sphaeroides (a nitrogen-fixing cyanobacterium) and Chlorella sorokiniana (a green alga) and their application in polyQ-mediated spinocerebellar ataxias (SCA). Firstly, the polysaccharides from these algae were examined for their 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radicals scavenging potential. The polysaccharides of these algae exhibited an effective scavenging capability on superoxide anion radical. Then their antioxidative activity was evaluated by measuring cellular production of reactive oxidative species (ROS) using CellRox green fluorescent probe on a flow cytometry. Pretreatment with polysaccharides from these algae protected both human embryonic kidney HEK-293 and neuroblastoma SH-SY5Y cells against the H2O2-induced cell death and reduced ROS production. Lastly, human SCA type 3 full length cDNAs with normal (ATXN3/Q14) and expanded (ATXN3/Q75) polyQ were constructed and transiently expressed in HEK-293T cells. Pre-treatment with algae polysaccharides significantly reduced ROS production in ATXN3/Q14~75 transfected cells. However, only fucoidan effectively enhanced hemeoxygenase (decycling) 1 (HMOX1) expression in ATXN3/Q75 expressing cells.