CDKL5障碍患者的血清脂质谱改变、SRB1缺失及Nrf2激活受损。
Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder.
作者信息
Pecorelli Alessandra, Belmonte Giuseppe, Meloni Ilaria, Cervellati Franco, Gardi Concetta, Sticozzi Claudia, De Felice Claudio, Signorini Cinzia, Cortelazzo Alessio, Leoncini Silvia, Ciccoli Lucia, Renieri Alessandra, Jay Forman Henry, Hayek Joussef, Valacchi Giuseppe
机构信息
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, "Santa Maria alle Scotte" General Hospital, Siena, Italy.
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
出版信息
Free Radic Biol Med. 2015 Sep;86:156-65. doi: 10.1016/j.freeradbiomed.2015.05.010. Epub 2015 May 22.
CDKL5 mutation is associated with an atypical Rett syndrome (RTT) variant. Recently, cholesterol homeostasis perturbation and oxidative-mediated loss of the high-density lipoprotein receptor SRB1 in typical RTT have been suggested. Here, we demonstrate an altered lipid serum profile also in CDKL5 patients with decreased levels of SRB1 and impaired activation of the defensive system Nrf2. In addition, CDKL5 fibroblasts showed an increase in 4-hydroxy-2-nonenal- and nitrotyrosine-SRB1 adducts that lead to its ubiquitination and probable degradation. This study highlights a possible common denominator between two different RTT variants (MECP2 and CDKL5) and a possible common future therapeutic target.
CDKL5突变与一种非典型雷特综合征（RTT）变体相关。最近，有人提出典型RTT中存在胆固醇稳态紊乱以及高密度脂蛋白受体SRB1的氧化介导性丧失。在此，我们证明在CDKL5患者中也存在脂质血清谱改变，其SRB1水平降低且防御系统Nrf2的激活受损。此外，CDKL5成纤维细胞显示4-羟基-2-壬烯醛和硝基酪氨酸-SRB1加合物增加，这导致其泛素化并可能降解。本研究突出了两种不同RTT变体（MECP2和CDKL5）之间可能的共同特征以及一个可能的共同未来治疗靶点。
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