Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003, Barcelona, Spain.
Sci Rep. 2020 Sep 29;10(1):16023. doi: 10.1038/s41598-020-72625-z.
Down syndrome (DS) is the main genetic cause of intellectual disability due to triplication of human chromosome 21 (HSA21). Although there is no treatment for intellectual disability, environmental enrichment (EE) and the administration of green tea extracts containing epigallocatechin-3-gallate (EGCG) improve cognition in mouse models and individuals with DS. Using proteome, and phosphoproteome analysis in the hippocampi of a DS mouse model (Ts65Dn), we investigated the possible mechanisms underlying the effects of green tea extracts, EE and their combination. Our results revealed disturbances in cognitive-related (synaptic proteins, neuronal projection, neuron development, microtubule), GTPase/kinase activity and chromatin proteins. Green tea extracts, EE, and their combination restored more than 70% of the phosphoprotein deregulation in Ts65Dn, and induced possible compensatory effects. Our downstream analyses indicate that re-establishment of a proper epigenetic state and rescue of the kinome deregulation may contribute to the cognitive rescue induced by green tea extracts.
唐氏综合征（DS）是人类 21 号染色体（HSA21）三倍体导致智力障碍的主要遗传原因。虽然没有治疗智力障碍的方法，但环境富集（EE）和服用含有表没食子儿茶素没食子酸酯（EGCG）的绿茶提取物可以改善小鼠模型和 DS 个体的认知能力。通过对 DS 小鼠模型（Ts65Dn）海马的蛋白质组和磷酸化蛋白质组分析，我们研究了绿茶提取物、EE 及其组合的作用的可能机制。我们的结果揭示了认知相关（突触蛋白、神经元投射、神经元发育、微管）、GTPase/激酶活性和染色质蛋白的紊乱。绿茶提取物、EE 及其组合恢复了 Ts65Dn 中超过 70%的磷酸化蛋白失调，并诱导了可能的补偿效应。我们的下游分析表明，适当的表观遗传状态的重建和激酶组失调的挽救可能有助于绿茶提取物诱导的认知恢复。
