Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease
It has been suggested that aggregation of α-synuclein (α-syn) into oligomers leads to neurodegeneration in Parkinson's disease (PD), but intravenous immunoglobulin (IVIG) which contains antibodies against α-syn monomers and oligomers fails to treat PD mouse model. The reason may be because IVIG...
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Elsevier
2019-04-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996118304017 |
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author | Ya-ru Huang Xi-xiu Xie Mei Ji Xiao-lin Yu Jie Zhu Ling-xiao Zhang Xiao-ge Liu Chen Wei Gang Li Rui-tian Liu |
author_facet | Ya-ru Huang Xi-xiu Xie Mei Ji Xiao-lin Yu Jie Zhu Ling-xiao Zhang Xiao-ge Liu Chen Wei Gang Li Rui-tian Liu |
author_sort | Ya-ru Huang |
collection | DOAJ |
description | It has been suggested that aggregation of α-synuclein (α-syn) into oligomers leads to neurodegeneration in Parkinson's disease (PD), but intravenous immunoglobulin (IVIG) which contains antibodies against α-syn monomers and oligomers fails to treat PD mouse model. The reason may be because IVIG contains much low level of antibodies against α-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 α-syn (NAbs-α-syn) from IVIG. Our further investigation results showed that NAbs-α-syn inhibited α-syn aggregation and attenuated α-syn-induced cytotoxicity in vitro. Compared with vehicles, NAbs-α-syn significantly attenuated the memory and motor deficits by reducing the levels of soluble α-syn, total human α-syn and α-syn oligomers, decreasing the intracellular p-α-synser129 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-α-syn overcomes the deficiency of IVIG and exhibits a promising therapeutic potential for the treatment of PD. |
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id | doaj.art-e32fd0b6658847ebacb36342141d1ef6 |
institution | Directory Open Access Journal |
issn | 1095-953X |
language | English |
last_indexed | 2024-12-15T00:07:58Z |
publishDate | 2019-04-01 |
publisher | Elsevier |
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series | Neurobiology of Disease |
spelling | doaj.art-e32fd0b6658847ebacb36342141d1ef62022-12-21T22:42:41ZengElsevierNeurobiology of Disease1095-953X2019-04-01124202217Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's diseaseYa-ru Huang0Xi-xiu Xie1Mei Ji2Xiao-lin Yu3Jie Zhu4Ling-xiao Zhang5Xiao-ge Liu6Chen Wei7Gang Li8Rui-tian Liu9National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, ChinaNational Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, ChinaNational Institutes for Food and Drug Control, Beijing 100050, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan 430022, China; Corresponding authors.National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China; Corresponding authors.It has been suggested that aggregation of α-synuclein (α-syn) into oligomers leads to neurodegeneration in Parkinson's disease (PD), but intravenous immunoglobulin (IVIG) which contains antibodies against α-syn monomers and oligomers fails to treat PD mouse model. The reason may be because IVIG contains much low level of antibodies against α-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 α-syn (NAbs-α-syn) from IVIG. Our further investigation results showed that NAbs-α-syn inhibited α-syn aggregation and attenuated α-syn-induced cytotoxicity in vitro. Compared with vehicles, NAbs-α-syn significantly attenuated the memory and motor deficits by reducing the levels of soluble α-syn, total human α-syn and α-syn oligomers, decreasing the intracellular p-α-synser129 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-α-syn overcomes the deficiency of IVIG and exhibits a promising therapeutic potential for the treatment of PD.http://www.sciencedirect.com/science/article/pii/S0969996118304017Parkinson's diseaseα-SynucleinNaturally occurring autoantibodiesA53T miceIVIG |
spellingShingle | Ya-ru Huang Xi-xiu Xie Mei Ji Xiao-lin Yu Jie Zhu Ling-xiao Zhang Xiao-ge Liu Chen Wei Gang Li Rui-tian Liu Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease Neurobiology of Disease Parkinson's disease α-Synuclein Naturally occurring autoantibodies A53T mice IVIG |
title | Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease |
title_full | Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease |
title_fullStr | Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease |
title_full_unstemmed | Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease |
title_short | Naturally occurring autoantibodies against α-synuclein rescues memory and motor deficits and attenuates α-synuclein pathology in mouse model of Parkinson's disease |
title_sort | naturally occurring autoantibodies against α synuclein rescues memory and motor deficits and attenuates α synuclein pathology in mouse model of parkinson s disease |
topic | Parkinson's disease α-Synuclein Naturally occurring autoantibodies A53T mice IVIG |
url | http://www.sciencedirect.com/science/article/pii/S0969996118304017 |
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