Differential seeding and propagating efficiency ofα-synuclein strains generated in different conditions  

作　　者：Di Liu Jian-Jun Guo Ji-Hui Su Alexander Svanbergsson Lin Yuan Caroline Haikal Wen Li Gunnar Gouras Jia-Yi Li 

机构地区：[1]Institute of Neuroscience,College of Life and Health Sciences,Northeastern University,Shenyang 110169,China [2]Neural Plasticity and Repair Unit,Wallenberg Neuroscience Center,Lund University,BMC A10,22184 Lund,Sweden [3]Experimental Dementia Research,Lund University,BMC B11,22184 Lund,Sweden [4]Institute of Health Sciences,China Medical University,Shenyang 110122,China

出　　处：《Translational Neurodegeneration》2021年第2期257-271,共15页转化神经变性病（英文）

基　　金：Financial supports of JYL lab by the National Key Research and Development Program of China(2018YFA0108500);the National Natural Science Foundation(81430025,81701265,31800898,U1801681);the Key Field Research Development Program of Gungdong Province(2018B030337001);Financial supports of JYL lab by the Swedish Research Council(521-2014-3257,2019-01551);EU-JPND(aSynProtec)and EU-JPND(REfrAME);EU H2020-MSCA-ITN-2016(Syndegen);the Strong Research Environment MultiPark(Multidisciplinary research on Parkinson’s disease);Parkinsonfonden and Olle Engkvist Byggmästare Foundation.DL was supported by China Scholarship Council.Open Access funding provided by Lund University。

摘　　要：Background:Accumulation of alpha-synuclein(α-syn)is a main pathological hallmark of Parkinson’s and related diseases,which are collectively known as synucleinopathies.Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes,suggesting the existence of strain difference amongα-syn fibrils.Previous studies have shown thatα-syn pathology can propagate from the peripheral nervous system(PNS)to the central nervous system(CNS)in a“prion-like”manner.However,the difference of the propagation potency from the periphery to CNS among differentα-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail.Methods:Three strains of preformedα-syn fibrils(PFFs)were generated in different buffer conditions which varied in pH and ionic concentrations.Theα-syn PFFs were intramuscularly(IM)injected into a novel bacterial artificial chromosome(BAC)transgenic mouse line that expresses wild-type humanα-syn,and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated.Results:The three strains ofα-syn PFFs triggered distinct propagation patterns.The fibrils generated in mildly acidic buffer led to the most severeα-syn pathology,degeneration of motor neurons and microgliosis in the spinal cord.Conclusions:The differentα-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS,which further supports the view thatα-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies.

关 键 词：Α-SYNUCLEIN STRAINS Prion-like propagation Parkinson’s disease 

分 类 号：R742.5[医药卫生—神经病学与精神病学]