Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Departments of Neurology, Neuroscience, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Mov Disord. 2019 May;34(5):614-624. doi: 10.1002/mds.27631. Epub 2019 Feb 6.
Lysosomal storage disorders comprise a clinically heterogeneous group of autosomal-recessive or X-linked genetic syndromes caused by disruption of lysosomal biogenesis or function resulting in accumulation of nondegraded substrates. Although lysosomal storage disorders are diagnosed predominantly in children, many show variable expressivity with clinical presentations possible later in life. Given the important role of lysosomes in neuronal homeostasis, neurological manifestations, including movement disorders, can accompany many lysosomal storage disorders. Over the last decade, evidence from genetics, clinical epidemiology, cell biology, and biochemistry have converged to implicate links between lysosomal storage disorders and adult-onset movement disorders. The strongest evidence comes from mutations in Glucocerebrosidase, which cause Gaucher's disease and are among the most common and potent risk factors for PD. However, recently, many additional lysosomal storage disorder genes have been similarly implicated, including SMPD1, ATP13A2, GALC, and others. Examination of these links can offer insight into pathogenesis of PD and guide development of new therapeutic strategies. We systematically review the emerging genetic links between lysosomal storage disorders and PD. © 2019 International Parkinson and Movement Disorder Society.
溶酶体贮积症是一组临床异质性的常染色体隐性或 X 连锁遗传综合征，由溶酶体发生或功能障碍引起，导致非降解底物的积累。虽然溶酶体贮积症主要在儿童中诊断，但许多疾病具有可变的表达性，临床表现可能在以后的生活中出现。鉴于溶酶体在神经元稳态中的重要作用，许多溶酶体贮积症可伴有神经表现，包括运动障碍。在过去十年中，遗传学、临床流行病学、细胞生物学和生物化学的证据已经证实溶酶体贮积症与成人发病的运动障碍之间存在关联。最有力的证据来自于葡萄糖脑苷脂酶的突变，这些突变导致戈谢病，是 PD 最常见和最有力的危险因素之一。然而，最近，许多其他溶酶体贮积症基因也同样被牵连，包括 SMPD1、ATP13A2、GALC 等。对这些联系的研究可以深入了解 PD 的发病机制，并指导新的治疗策略的发展。我们系统地综述了溶酶体贮积症与 PD 之间新出现的遗传联系。 © 2019 国际帕金森病和运动障碍协会。
