Liu Elaine A, Lieberman Andrew P
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Cellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, United States.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, United States.
Neurosci Lett. 2019 Apr 1;697:10-16. doi: 10.1016/j.neulet.2018.04.049. Epub 2018 Apr 25.
The lysosomal storage disorders (LSDs) encompass a group of more than 50 inherited diseases characterized by the accumulation of lysosomal substrates. Two-thirds of patients experience significant neurological symptoms, but the mechanisms of neurodegeneration are not well understood. Interestingly, a wide range of LSDs show defects in both autophagy and Ca homeostasis, which is notable as Ca is a key regulator of autophagy. The crosstalk between these pathways in the context of LSD pathogenesis is not well characterized, but further understanding of this relationship could open up promising therapeutic targets. This review discusses the role of endoplasmic reticulum and lysosomal Ca in autophagy regulation and highlights what is known about defects in autophagy and Ca homeostasis in two LSDs, Niemann-Pick type C disease and Gaucher disease.
溶酶体贮积症（LSDs）包括50多种遗传性疾病，其特征是溶酶体底物的积累。三分之二的患者会出现明显的神经症状，但神经退行性变的机制尚不清楚。有趣的是，多种溶酶体贮积症在自噬和钙稳态方面均表现出缺陷，鉴于钙是自噬的关键调节因子，这一点值得关注。在溶酶体贮积症发病机制中，这些途径之间的相互作用尚未得到充分描述，但对这种关系的进一步了解可能会开辟有前景的治疗靶点。本综述讨论了内质网和溶酶体钙在自噬调节中的作用，并着重介绍了在两种溶酶体贮积症——尼曼-匹克C型病和戈谢病中，关于自噬和钙稳态缺陷的已知情况。
