An exciting development in the field of neurodegeneration is the association between the rare monogenic disorder Gaucher disease and the common complex disorder Parkinson disease (PD). Gaucher disease is a lysosomal storage disorder resulting from an inherited deficiency of the enzyme glucocerebrosidase, encoded by GBA1, which hydrolyses the glycosphingolipids glucosylceramide and glucosylsphingosine. The observation of parkinsonism in a rare subgroup of individuals with Gaucher disease first directed attention to the role of glucocerebrosidase deficiency in the pathogenesis of PD. PD occurs more frequently in people heterozygous for Gaucher GBA1 mutations, and 3–25% of people with Parkinson disease carry a GBA1 variant. However, only a small percentage of individuals with GBA1 variants develop parkinsonism, suggesting that the penetrance is low. Despite over a decade of intense research in this field, including clinical and radiological evaluations, genetic studies and investigations using model systems, the mechanism underlying GBA1-PD is still being pursued. Insights from this association have emphasized the role of lysosomal pathways in parkinsonism. Furthermore, different therapeutic strategies considered or developed for Gaucher disease can now inform drug development for PD.

神经退行性疾病领域的一个令人兴奋的进展是罕见的单基因疾病戈谢病和常见的复杂疾病帕金森病 (PD) 之间的关联。戈谢病是一种溶酶体贮积症，由GBA1编码的葡萄糖脑苷脂酶遗传性缺陷所致，该酶可水解鞘糖脂葡萄糖神经酰胺和葡萄糖基鞘氨醇。在戈谢病患者的罕见亚群中观察到帕金森病，首先引起人们对葡萄糖脑苷脂酶缺乏在帕金森病发病机制中的作用的关注。 PD 在戈谢GBA1突变杂合子人群中更常见，3-25% 的帕金森病患者携带GBA1突变。然而，只有一小部分携带GBA1变异的个体会患上帕金森症，这表明外显率较低。尽管在这一领域进行了十多年的深入研究，包括临床和放射学评估、基因研究和使用模型系统的调查，但GBA1 -PD 的潜在机制仍在探索中。该协会的见解强调了溶酶体途径在帕金森病中的作用。此外，针对戈谢病考虑或开发的不同治疗策略现在可以为帕金森病的药物开发提供信息。