Department of Paediatrics and Adolescent Medicine, Biochemistry and Molecular Genetics, American University of Beirut, PO Box 11-0236, Riad El-Solh, 1107 2020, Beirut, Lebanon.
Nat Rev Neurol. 2013 Oct;9(10):583-98. doi: 10.1038/nrneurol.2013.163. Epub 2013 Aug 13.
Since the discovery of the lysosome in 1955, advances have been made in understanding the key roles and functions of this organelle. The concept of lysosomal storage diseases (LSDs)--disorders characterized by aberrant, excessive storage of cellular material in lysosomes--developed following the discovery of α-glucosidase deficiency as the cause of Pompe disease in 1963. Great strides have since been made in understanding the pathobiology of LSDs and the neuronal ceroid lipofuscinoses (NCLs). The NCLs are neurodegenerative disorders that display symptoms of cognitive and motor decline, seizures, blindness, early death, and accumulation of lipofuscin in various cell types, and also show some similarities to 'classic' LSDs. Defective lysosomal storage can occur in many cell types, but the CNS and PNS are particularly vulnerable to LSDs and NCLs, being affected in two-thirds of these disorders. Most LSDs are inherited in an autosomal recessive manner, with the exception of X-linked Hunter disease, Fabry disease and Danon disease, and a variant type of adult NCL (Kuf disease). This Review provides a summary of known LSDs, and the pathways affected in these disorders. Existing therapies and barriers to development of novel and improved treatments for LSDs and NCLs are also discussed.
自 1955 年发现溶酶体以来，人们对该细胞器的关键作用和功能的理解取得了进展。1963 年发现α-葡萄糖苷酶缺乏是庞贝病的病因后，溶酶体贮积症（LSDs）——以溶酶体中细胞物质异常、过度贮积为特征的疾病——的概念得以发展。此后，人们在理解 LSDs 和神经鞘脂褐素沉积症（NCLs）的病理生物学方面取得了巨大进展。NCLs 是神经退行性疾病，表现为认知和运动能力下降、癫痫、失明、早逝以及各种细胞类型中脂褐素的积累，并且与“经典”LSDs 也有一些相似之处。溶酶体贮积缺陷可发生在许多细胞类型中，但中枢神经系统和周围神经系统特别容易受到 LSDs 和 NCLs 的影响，在这些疾病中有三分之二受到影响。大多数 LSDs 以常染色体隐性方式遗传，除 X 连锁亨特病、法布雷病和 Danon 病以及一种变异型成人 NCL（Kuf 病）外。本文综述了已知的 LSDs 以及这些疾病中受影响的途径。还讨论了 LSDs 和 NCLs 的现有治疗方法以及开发新型和改进治疗方法的障碍。
