小柯机器人

美国Van Andel研究所Viviane Labrie团队通过帕金森氏病神经元的表观基因组学分析发现，Tet2丢失具有神经保护作用。相关论文于2020年8月17日在线发表在《自然—神经科学》杂志上。

Title: Epigenomic analysis of Parkinson’s disease neurons identifies Tet2 loss as neuroprotective

Author: Lee L. Marshall, Bryan A. Killinger, Elizabeth Ensink, Peipei Li, Katie X. Li, Wei Cui, Noah Lubben, Matthew Weiland, Xinhe Wang, Juozas Gordevicius, Gerhard A. Coetzee, Jiyan Ma, Stefan Jovinge, Viviane Labrie

Issue&Volume: 2020-08-17

Abstract: Parkinson’s disease (PD) pathogenesis may involve the epigenetic control of enhancers that modify neuronal functions. Here, we comprehensively examine DNA methylation at enhancers, genome-wide, in neurons of patients with PD and of control individuals. We find a widespread increase in cytosine modifications at enhancers in PD neurons, which is partly explained by elevated hydroxymethylation levels. In particular, patients with PD exhibit an epigenetic and transcriptional upregulation of TET2, a master-regulator of cytosine modification status. TET2 depletion in a neuronal cell model results in cytosine modification changes that are reciprocal to those observed in PD neurons. Moreover, Tet2 inactivation in mice fully prevents nigral dopaminergic neuronal loss induced by previous inflammation. Tet2 loss also attenuates transcriptional immune responses to an inflammatory trigger. Thus, widespread epigenetic dysregulation of enhancers in PD neurons may, in part, be mediated by increased TET2 expression. Decreased Tet2 activity is neuroprotective, in vivo, and may be a new therapeutic target for PD.

DOI: 10.1038/s41593-020-0690-y

Source: https://www.nature.com/articles/s41593-020-0690-y

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex