诸如阿尔茨海默氏病、多发性硬化症与散发性克—雅氏病（疯牛病）等破坏神经细胞的疾病，对科学家来说始终难以捉摸，更是难以治愈。最近，美国密歇根大学科研人员发现了一种不知名的信号分子与神经细胞健康之间的联系，这有望解释神经细胞退化的原因。该科研成果发表在近期出版的《美国国家科学院院刊》杂志上。
在该项研究中，美国生命科学学院教授洛伊斯·威斯曼及其助手将这种信号分子与脑部大量的神经细胞退化联系起来。这种被称为PI(3,5)P2（磷脂酰肌醇-3,5-二磷酸的简称）的分子存在于所有细胞中，是一种浓度很低的脂质。
信号脂质PI(3,5)P2是生物信息系统的一部分，这种信息系统不仅可感知细胞外的变化，也可促进细胞内部活动以使细胞适应该变化，是一类非常独特的脂质，承担着信号分子的特殊使命。而产生脂质的酶由酵母基因FIG4与VAC14基因控制，这两种基因不仅存在于酵母菌，也同样存在于老鼠和人类体内。VAC14是对PI(3,5)P2浓度进行编码的基因。威斯曼发现，缺乏VAC14的老鼠神经系统严重退化，而这种退化看起来类似于那些FIG4发生突变的老鼠的神经细胞的退化，一旦VAC14基因被移除，很多神经元细胞的本体内就会出现空洞空间，大脑则呈现海绵状。
威斯曼表示，PI(3,5)P2对于神经系统细胞的存活起了关键性作用，较低浓度的PI(3,5)P2可导致重度的神经细胞退化，这一发现预示着可以更好地研究如阿尔茨海默氏病等神经细胞退化性疾病的疗法。（科技日报）
原始出处:
Published online before print October 23, 2007, 10.1073/pnas.0702275104
PNAS | October 30, 2007 | vol. 104 | no. 44 | 17518-17523
Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice
Yanling Zhang*,, Sergey N. Zolov*, Clement Y. Chow, Shalom G. Slutsky, Simon C. Richardson¶, Robert C. Piper¶, Baoli Yang||, Johnathan J. Nau, Randal J. Westrick, Sean J. Morrison, Miriam H. Meisler, and Lois S. Weisman*,**,
*Life Sciences Institute, Department of Human Genetics, **Department of Cellular and Developmental Biology, and Howard Hughes Medical Institute and Department of Internal Medicine and Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109; and Departments of Biochemistry, ¶Physiology, and ||Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242
Edited by Pietro V. De Camilli, Yale University School of Medicine, New Haven, CT, and approved September 17, 2007 (received for review March 12, 2007)
The signaling lipid, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), likely functions in multiple signaling pathways. Here, we report the characterization of a mouse mutant lacking Vac14, a regulator of PI(3,5)P2 synthesis. The mutant mice exhibit massive neurodegeneration, particularly in the midbrain and in peripheral sensory neurons. Cell bodies of affected neurons are vacuolated, and apparently empty spaces are present in areas where neurons should be present. Similar vacuoles are found in cultured neurons and fibroblasts. Selective membrane trafficking pathways, especially endosome-to-TGN retrograde trafficking, are defective. This report, along with a recent report on a mouse with a null mutation in Fig4, presents the unexpected finding that the housekeeping lipid, PI(3,5)P2, is critical for the survival of neural cells.
Fab1 | PIKfyve | PtdInsI(3,5)P2 | spongiform | endosomal traffic
