Department of Physiology and National University Medical Institutes, Yong Loo Lin School of Medicine, and Neurobiology Programme, Life Science Institute, National University of Singapore, Singapore.
J Neurochem. 2010 Mar;112(6):1619-26. doi: 10.1111/j.1471-4159.2010.06586.x. Epub 2010 Jan 13.
Neurodegeneration is the final cause of death in Niemann-Pick Type C (NPC) disease, a cholesterol-storage disorder. Accumulating evidence indicates that NPC may share common pathological mechanisms with Alzheimer's disease, including the link between aberrant cholesterol metabolism and amyloid-beta (Abeta) deposition. Apolipoprotein E (apoE) is highly expressed in the brain and plays a pivotal role in cholesterol metabolism. ApoE can also modulate Abeta production and clearance, and it is a major genetic risk factor for Alzheimer's disease. Although apoE is glycosylated, the functional significance of this chemical alteration on Abeta catabolism is unclear. In this study using an NPC animal model, we detect specific changes in apoE glycosylation that correlate with increased Abeta(42) accumulation prior to the appearance of neurological abnormalities. This suggests that increased apoE expression could be a compensatory response to the increased Abeta(42) deposition in NPC(nih) mice. We also observe what appears to be a simplification of the glycosylation process on apoE during neurodegeneration.
神经退行性变是尼曼-匹克 C 型（NPC）疾病的最终死亡原因，这是一种胆固醇贮积病。越来越多的证据表明，NPC 可能与阿尔茨海默病具有共同的病理机制，包括异常胆固醇代谢与淀粉样β（Abeta）沉积之间的联系。载脂蛋白 E（apoE）在大脑中高度表达，在胆固醇代谢中发挥关键作用。ApoE 还可以调节 Abeta 的产生和清除，并且是阿尔茨海默病的主要遗传风险因素。尽管 apoE 发生了糖基化，但这种化学改变对 Abeta 代谢的功能意义尚不清楚。在这项使用 NPC 动物模型的研究中，我们检测到 apoE 糖基化的特定变化，这些变化与神经功能异常出现之前 Abeta(42)积累的增加相关。这表明，apoE 表达的增加可能是 NPC 小鼠中 Abeta(42)沉积增加的代偿反应。我们还观察到，在神经退行性变过程中，apoE 的糖基化过程似乎变得简化。
