Ariga Toshio
Institute of Molecular Medicine and Genetics, Institute of Neuroscience, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
J Neurosci Res. 2014 Oct;92(10):1227-42. doi: 10.1002/jnr.23411. Epub 2014 Jun 5.
Ganglioside metabolism is altered in several neurodegenerative diseases, and this may participate in several events related to the pathogenesis of these diseases. Most changes occur in specific areas of the brain and their distinct membrane microdomains or lipid rafts. Antiganglioside antibodies may be involved in dysfunction of the blood-brain barrier and disease progression in these diseases. In lipid rafts, interactions of glycosphingolipids, including ganglioside, with proteins may be responsible for the misfolding events that cause the fibril and/or aggregate processing of disease-specific proteins, such as α-synuclein, in Parkinson's disease, huntingtin protein in Huntington's disease, and copper-zinc superoxide dismutase in amyotrophic lateral sclerosis. Targeting ganglioside metabolism may represent an underexploited opportunity to design novel therapeutic strategies for neurodegeneration in these diseases.
神经节苷脂代谢在几种神经退行性疾病中发生改变，这可能参与了与这些疾病发病机制相关的多个事件。大多数变化发生在大脑的特定区域及其独特的膜微区或脂筏中。抗神经节苷脂抗体可能参与这些疾病中血脑屏障的功能障碍和疾病进展。在脂筏中，包括神经节苷脂在内的糖鞘脂与蛋白质的相互作用可能是导致疾病特异性蛋白质（如帕金森病中的α-突触核蛋白、亨廷顿病中的亨廷顿蛋白和肌萎缩侧索硬化症中的铜锌超氧化物歧化酶）发生错误折叠事件从而形成原纤维和/或聚集体的原因。针对神经节苷脂代谢可能是为这些疾病中的神经退行性变设计新型治疗策略的一个尚未充分利用的机会。
