國家衛生研究院 NHRI:Item 3990099045/13574
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    题名: Administration of AAV-alpha synuclein NAC antibody improves locomotor behavior in rats overexpressing alpha synuclein
    其它题名: Administration of AAV-α synuclein NAC antibody improves locomotor behavior in rats overexpressing α synuclein
    作者: Chen, YH;Wu, KJ;Hsieh, W;Harvey, BK;Hoffer, BJ;Wang, Y;Yu, SJ
    贡献者: Center for Neuropsychiatric Research
    摘要: Accumulation of α-Synuclein (αSyn) in nigral dopaminergic neurons is commonly seen in patients with Parkinson's disease (PD). We recently reported that transduction of intracellular single-chain intrabody targeting the 53-87 amino acid residues of human αSyn by recombinant adeno associated viral vector (AAV-NAC32) downregulated αSyn protein in SH-SY5Y cells and rat brain. This study characterizes the behavioral phenotype and dopaminergic protection in animals receiving AAV-NAC32. Our results show that adult DAT-Cre rats selectively overexpress αSyn in nigra dopaminergic neurons after local administration of AAV-DIO-αSyn. These animals develop PD-like phenotype, including bradykinesia and loss of tyrosine hydroxylase (TH) immunoreactivity in substantia nigra pars compacta dorsal tier (SNcd). An injection of AAV-NAC32 to nigra produces a selective antibody against αSyn and normalizes the behavior. AAV-NAC32 significantly increases TH, while reduces αSyn immunoreactivity in SNcd. Altogether, our data suggest that an AAV-mediated gene transfer of NAC32 antibody effectively antagonizes αSyn-mediated dopaminergic degeneration in nigra, which may be a promising therapeutic candidate for synucleinopathy or PD.
    日期: 2021-06-21
    關聯: Genes. 2021 Jun 21;12(6):Article number 948.
    Link to: http://dx.doi.org/10.3390/genes12060948
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2073-4425&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000666169500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85108684277
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