期刊
ACTA NEUROPATHOLOGICA COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s40478-016-0410-8
关键词
alpha-synuclein; Animal model; Axonal transport; Immunization; Synucleinopathy
资金
- NIH [AG18840, NS044233, BX003040, AG0051839, AG10483, AG005131]
- Prothena Biosciences
Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of alpha-synuclein (alpha-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of alpha-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of alpha-syn reduce the intra-neuronal accumulation of alpha-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of alpha-syn in in vivo models. Here, we assessed the effect of passive immunization against alpha-syn in a new mouse model of axonal transport and accumulation of alpha-syn. For these purpose, non-transgenic, alpha-syn knock-out and mThy1-alpha-syn tg (line 61) mice received unilateral intra-cerebral injections with a lentiviral (LV)-alpha-syn vector construct followed by systemic administration of the monoclonal antibody 1H7 (recognizes amino acids 91-99) or control IgG for 3 months. Cerebral alpha-syn accumulation and axonopathy was assessed by immunohistochemistry and effects on behavior were assessed by Morris water maze. Unilateral LV-alpha-syn injection resulted in axonal propagation of alpha-syn in the contra-lateral site with subsequent behavioral deficits and axonal degeneration. Passive immunization with 1H7 antibody reduced the axonal accumulation of alpha-syn in the contra-lateral side and ameliorated the behavioral deficits. Together this study supports the notion that immunotherapy might improve the deficits in models of synucleinopathy by reducing the axonal propagation and accumulation of alpha-syn. This represents a potential new mode of action through which alpha-syn immunization might work.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据