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图片来源：medicalxpress.com
2015年11月19日 讯 /生物谷BIOON/ –近日，来自耶鲁大学等处的一项最新研究报告指出，控制脂质代谢的一种基因的突变或可引发一种以髓鞘为标志的缓慢进行性的神经性遗传疾病，相关研究或为揭示控制多发性硬化的新型疗法提供思路，该研究刊登于国际杂志Nature Cell Biology上。
文章中，研究者指出，名为FAM126A的单一基因的突变会引发一系列的病理学病变，比如发育延缓、智力障碍、周围神经病变及肌肉萎缩等，此外还会引发先天性的白内障，然而截至目前研究者并不清楚该基因的精确功能。
研究人员Pietro De Camilli表示，我们发现，FAM126A基因编码的蛋白hyccin可以帮助产生一种对髓鞘形成非常重要的脂质，在整个神经系统中髓鞘可以包围并且保护神经元细胞中的轴突；这项研究中研究人员联合美国、意大利等多国的研究人员对髓鞘形成减少症和先天性白内障患者机体的细胞进行分析发现，基因FAM126A的突变会导致对髓磷脂产生非常重要的酶类复合物失去稳定性。
在多发性硬化症患者中，疾病的进展主要依赖于髓鞘的再度生成，而患者机体的免疫系统常常会对髓鞘进行攻击，最终引发神经元死亡；文章中研究者推测，在机体正常发育和多发性硬化症患者恢复阶段，hyccin对于髓鞘的产生发挥着至关重要的作用；后期研究中研究人员或将对大量样本进行大范围研究，来为开发治疗多发性硬化症等神经性疾病的新型疗法提供研究依据。（基因宝jiyinbao.com）
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The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane
Jeremy M. Baskin, Xudong Wu, Romain Christiano, Michael S. Oh, Curtis M. Schauder, Elisabetta Gazzerro, Mirko Messa, Simona Baldassari, Stefania Assereto, Roberta Biancheri, Federico Zara, Carlo Minetti, Andrea Raimondi, Mikael Simons, Tobias C. Walther, Karin M. Reinisch & Pietro De Camilli
Genetic defects in myelin formation and maintenance cause leukodystrophies, a group of white matter diseases whose mechanistic underpinnings are poorly understood1, 2. Hypomyelination and congenital cataract (HCC), one of these disorders, is caused by mutations in FAM126A, a gene of unknown function3. We show that FAM126A, also known as hyccin, regulates the synthesis of phosphatidylinositol 4-phosphate (PtdIns(4)P), a determinant of plasma membrane identity4, 5, 6. HCC patient fibroblasts exhibit reduced PtdIns(4)P levels. FAM126A is an intrinsic component of the plasma membrane phosphatidylinositol 4-kinase complex that comprises PI4KIIIα and its adaptors TTC7 and EFR3 (refs 5,7). A FAM126A–TTC7 co-crystal structure reveals an all-α-helical heterodimer with a large protein–protein interface and a conserved surface that may mediate binding to PI4KIIIα. Absence of FAM126A, the predominant FAM126 isoform in oligodendrocytes, destabilizes the PI4KIIIα complex in mouse brain and patient fibroblasts. We propose that HCC pathogenesis involves defects in PtdIns(4)P production in oligodendrocytes, whose specialized function requires massive plasma membrane expansion and thus generation of PtdIns(4)P and downstream phosphoinositides8, 9, 10, 11. Our results point to a role for FAM126A in supporting myelination, an important process in development and also following acute exacerbations in multiple sclerosis12, 13, 14.