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Naturally occurring autoantibodies against alpha-synuclein rescues memory and motor deficits and attenuates alpha-synuclein pathology in mouse model of Parkinson's disease
Huang, Ya-ru1,2; Xie, Xi-xiu1; Ji, Mei1,2; Yu, Xiao-lin1; Zhu, Jie1; Zhang, Ling-xiao1,2; Liu, Xiao-ge1,2; Wei, Chen3; Li, Gang4; Liu, Rui-tian1
2019-04-01
Source PublicationNEUROBIOLOGY OF DISEASE
ISSN0969-9961
Volume124Pages:202-217
AbstractIt has been suggested that aggregation of alpha-synuclein (alpha-syn) into oligomers leads to neurodegeneration in Parkinson's disease (PD), but intravenous immunoglobulin (IVIG) which contains antibodies against alpha-syn monomers and oligomers fails to treat PD mouse model. The reason may be because IVIG contains much low level of antibodies against alpha-syn, and of which only a small part can penetrate the blood-brain barrier, resulting in an extremely low level of effective antibodies in the brain, and limiting the beneficial effect of IVIG on PD mice. Here, we first isolated naturally occurring autoantibodies against alpha-syn (NAbs-alpha-syn) from IVIG. Our further investigation results showed that NAbs-alpha-syn inhibited alpha-syn aggregation and attenuated alpha-syn-induced cytotoxicity in vitro. Compared with vehicles, NAbs-alpha-syn significantly attenuated the memory and motor deficits by reducing the levels of soluble alpha-syn, total human alpha-syn and alpha-syn oligomers, decreasing the intracellular P-alpha-syn(ser129) deposits and axonal pathology, inhibiting the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines, increasing the levels of PSD95, synaptophysin and TH in the brain of A53T transgenic mice. These findings suggest that NAbs-alpha-syn overcomes the deficiency of IVIG and exhibits a promising therapeutic potential for the treatment of PD.
KeywordParkinson's disease alpha-Synuclein Naturally occurring autoantibodies A53T mice WIG
DOI10.1016/j.nbd.2018.11.024
Language英语
WOS KeywordINTRAVENOUS IMMUNOGLOBULIN ; ALZHEIMERS-DISEASE ; TRANSGENIC MODEL ; AGGREGATION ; IMMUNOTHERAPY ; ANTIBODIES ; OLIGOMERS ; MICE ; NEURODEGENERATION ; ACCUMULATION
Funding ProjectStrategic Leading Project of China Academy of Sciences[XDA 12040215] ; National Science and Technology Major Projects of New Drugs[2015ZX09102015]
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
Funding OrganizationStrategic Leading Project of China Academy of Sciences ; National Science and Technology Major Projects of New Drugs
WOS IDWOS:000459217800019
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/28087
Collection中国科学院过程工程研究所
Corresponding AuthorLi, Gang; Liu, Rui-tian
Affiliation1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Sch Chem Engn, Beijing 100049, Peoples R China
3.Natl Inst Food & Drug Control, Beijing 100050, Peoples R China
4.Huazhong Univ Sci & Technol, Union Hosp, Dept Neurol, Tongji Med Coll, Jiefang Ave, Wuhan 430022, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Huang, Ya-ru,Xie, Xi-xiu,Ji, Mei,et al. Naturally occurring autoantibodies against alpha-synuclein rescues memory and motor deficits and attenuates alpha-synuclein pathology in mouse model of Parkinson's disease[J]. NEUROBIOLOGY OF DISEASE,2019,124:202-217.
APA Huang, Ya-ru.,Xie, Xi-xiu.,Ji, Mei.,Yu, Xiao-lin.,Zhu, Jie.,...&Liu, Rui-tian.(2019).Naturally occurring autoantibodies against alpha-synuclein rescues memory and motor deficits and attenuates alpha-synuclein pathology in mouse model of Parkinson's disease.NEUROBIOLOGY OF DISEASE,124,202-217.
MLA Huang, Ya-ru,et al."Naturally occurring autoantibodies against alpha-synuclein rescues memory and motor deficits and attenuates alpha-synuclein pathology in mouse model of Parkinson's disease".NEUROBIOLOGY OF DISEASE 124(2019):202-217.
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