Shiitake-derived lentinan preventsα-synuclein aggregation,disassembles amyloid aggregates,and protects dopaminergic neurons  

香菇多糖能够有效抑制α突触核蛋白聚集、解组装淀粉样蛋白聚集体并保护多巴胺能神经元

作　　者：Fanling Meng Yanan Li Siyu Wang Yanni Pan Shangbang Gao Liang Luo 孟凡玲;李亚楠;王思予;潘彦妮;高尚邦;罗亮

机构地区：[1]National Engineering Research Center for Nanomedicine,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China [2]Key Laboratory of Molecular Biophysics of the Ministry of Education,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China

出　　处：《Science China Materials》2024年第12期3898-3907,共10页中国科学（材料科学）（英文版）

基　　金：supported by the National Natural Science Foundation of China(22077038,22477032,32371189);National Undergraduate Innovation and Entrepreneurship Research Practice Program(201910487066);Huazhong University of Science and Technology Supportive Fund for Basic Research。

摘　　要：Parkinson’s disease(PD)is the second largest degenerative disease of central nervous system around the world.α-Synuclein(α-syn)is the main component of Lewy body amyloid deposits in the brain of PD patients and associated with the pathogenesis of PD.α-Syn aggregates can induce neuron death and cause irreversible neurological damage.Therefore,the inhibition ofα-syn aggregation and removal of preformed amyloid fibers are important strategies for the prevention and treatment of PD.However,there is still a lack of potent inhibitors to interfere withα-syn aggregation.In this work,we demonstrate that lentinan(LNT),a natural polysaccharide extracted from the fruit body of Lentinula edodes,can potently preventα-syn aggregation,disassemble preformed amyloid aggregates,and suppressα-syn-mediated cell toxicity and reactive oxygen species generation.Interestingly,we also find that the molecular weight of the polysaccharide impacts the inhibitory effect of LNT.Further in vivo investigation demonstrates that LNT significantly inhibits the accumulation ofα-syn in nematodes C.elegans,relieves the symptoms of PD nematode motility disorders,and effectively protects dopaminergic neurons from C.elegans PD models.To the best of our knowledge,this is the first time to report that LNT can modulateα-syn aggregation in vitro and in vivo,which will provide new insights for designing and developing potential agents for PD treatment.帕金森病(Parkinson’s disease,PD)是全球第二大中枢神经系统退行性疾病.α-突触核蛋白(α-syn)是PD患者大脑中路易体淀粉样沉积的主要成分,并与PD的发病机制密切相关.α-syn聚集可以诱导神经元死亡并造成不可逆的神经系统损伤.因此,抑制α-syn的聚集和清除已形成的淀粉样聚集体对预防和治疗PD十分重要.然而,当前α-syn的聚集抑制剂有效性亟待提高.本文研究首次报道从香菇(Lentinula edodes)果体中提取的香菇多糖(LNT)可以有效预防α-syn的聚集,分解已形成的淀粉样聚集体,并抑制α-syn介导的细胞毒性和活性氧生成,且抑制效果受多糖分子量影响.体内研究进一步表明,LNT可显著抑制秀丽隐杆线虫中α-syn的积累,缓解PD线虫运动障碍的症状,并有效保护线虫PD模型中的多巴胺神经元,因此为设计和开发PD治疗的潜在药物提供了新思路.

关 键 词：Α-SYNUCLEIN protein aggregation inhibition LENTINAN DISASSEMBLY 

分 类 号：R742.5[医药卫生—神经病学与精神病学] TQ460.1[医药卫生—临床医学]