| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 124, Iss , Pp 202-217 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2018.11.024 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect