Vellodi Ashok
Metabolic Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK.
Br J Haematol. 2005 Feb;128(4):413-31. doi: 10.1111/j.1365-2141.2004.05293.x.
Although the first description of a lysosomal storage disorder was that of Tay-Sachs disease in 1881, the lysosome was not discovered until 1955, by Christian De Duve. The first demonstration by Hers in 1963 of a link between an enzyme deficiency and a storage disorder (Pompe's disease) paved the way for a series of seminal discoveries about the intracellular biology of these enzymes and their substrates, culminating in the successful treatment of Gaucher's disease with beta-glucosidase in the early 1990s. It is now recognized that these disorders are not simply a consequence of pure storage, but result from perturbation of complex cell signalling mechanisms. These in turn give rise to secondary structural and biochemical changes, which have important implications for therapy. Significant challenges remain, particularly the treatment of central nervous system disease. It is hoped that recent advances in our understanding of lysosomal biology will enable successful therapies to be developed.
尽管1881年就首次描述了溶酶体贮积症——泰-萨克斯病，但直到1955年克里斯蒂安·德·迪夫才发现溶酶体。1963年赫尔斯首次证明酶缺乏与贮积症（庞贝氏病）之间的联系，为一系列关于这些酶及其底物细胞内生物学的开创性发现铺平了道路，最终在20世纪90年代初用β-葡萄糖苷酶成功治疗了戈谢病。现在人们认识到，这些疾病不仅仅是单纯贮积的结果，而是复杂细胞信号传导机制受到干扰所致。这些反过来又引起继发性结构和生化变化，这对治疗具有重要意义。重大挑战依然存在，尤其是中枢神经系统疾病的治疗。希望我们对溶酶体生物学理解的最新进展能够促成成功疗法的开发。
