Laboratory of Functional Neurochemistry, IRCCS Mondino Foundation, Pavia, Italy.
Parkinson Institute, ASST Gaetano Pini-CTO, Milan, Italy.
Mov Disord. 2019 Jan;34(1):9-21. doi: 10.1002/mds.27583. Epub 2018 Dec 27.
Glucocerebrosidase is a lysosomal enzyme. The characterization of a direct link between mutations in the gene coding for glucocerebrosidase (GBA1) with the development of Parkinson's disease and dementia with Lewy bodies has heightened interest in this enzyme. Although the mechanisms through which glucocerebrosidase regulates the homeostasis of α-synuclein remains poorly understood, the identification of reduced glucocerebrosidase activity in the brains of patients with PD and dementia with Lewy bodies has paved the way for the development of novel therapeutic strategies directed at enhancing glucocerebrosidase activity and reducing α-synuclein burden, thereby slowing down or even preventing neuronal death. Here we reviewed the current literature relating to the mechanisms underlying the cross talk between glucocerebrosidase and α-synuclein, the GBA1 mutation-associated clinical phenotypes, and ongoing therapeutic approaches targeting glucocerebrosidase. © 2018 International Parkinson and Movement Disorder Society.
葡萄糖脑苷脂酶是溶酶体酶。编码葡萄糖脑苷脂酶（GBA1）的基因突变与帕金森病和路易体痴呆的发展之间存在直接联系的特征，这使得人们对这种酶产生了浓厚的兴趣。尽管葡萄糖脑苷脂酶调节α-突触核蛋白体内平衡的机制仍知之甚少，但在帕金森病和路易体痴呆患者的大脑中发现葡萄糖脑苷脂酶活性降低，为开发旨在增强葡萄糖脑苷脂酶活性和降低α-突触核蛋白负担的新型治疗策略铺平了道路，从而减缓甚至阻止神经元死亡。在这里，我们回顾了与葡萄糖脑苷脂酶和α-突触核蛋白之间的串扰、GBA1 突变相关的临床表型以及针对葡萄糖脑苷脂酶的正在进行的治疗方法相关的当前文献。 © 2018 国际帕金森病和运动障碍学会。
