Fabry disease: Mechanism and therapeutics strategies.
Fabry disease: Mechanism and therapeutics strategies.
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法布里病：机制和治疗策略
DOI：
10.3389/fphar.2022.1025740
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
法布里病是一种以α-半乳糖苷酶A（GLA）缺乏或缺失为特征的单基因疾病。由此导致的溶酶体GLA酶活性的损害导致酶底物的致病性积累，并因此导致靶器官（包括心脏、肾脏和大脑）中临床症状的逐渐出现。然而，涉及法布里病介导的器官损伤的机制在很大程度上是模糊的，知之甚少，这阻碍了治疗这种疾病的治疗策略的发展。尽管目前可用的临床方法在治疗法布里病方面显示出一定的效率，但它们都表现出需要克服的局限性。在这篇综述中，我们首先介绍了目前的法布里病的机制知识，并讨论其治疗的潜在治疗策略。然后，我们系统地总结和讨论治疗方法的研究进展，包括酶替代疗法（ERT），基因治疗和伴侣治疗，以及针对亚细胞区室，如溶酶体，内质网和细胞核的策略。最后，潜在的治疗策略的未来发展进行了讨论的基础上的机制研究的结果和与这些治疗方法的局限性。
Fabry disease is a monogenic disease characterized by a deficiency or loss of the α-galactosidase A (GLA). The resulting impairment in lysosomal GLA enzymatic activity leads to the pathogenic accumulation of enzymatic substrate and, consequently, the progressive appearance of clinical symptoms in target organs, including the heart, kidney, and brain. However, the mechanisms involved in Fabry disease-mediated organ damage are largely ambiguous and poorly understood, which hinders the development of therapeutic strategies for the treatment of this disorder. Although currently available clinical approaches have shown some efficiency in the treatment of Fabry disease, they all exhibit limitations that need to be overcome. In this review, we first introduce current mechanistic knowledge of Fabry disease and discuss potential therapeutic strategies for its treatment. We then systemically summarize and discuss advances in research on therapeutic approaches, including enzyme replacement therapy (ERT), gene therapy, and chaperone therapy, as well as strategies targeting subcellular compartments, such as lysosomes, the endoplasmic reticulum, and the nucleus. Finally, the future development of potential therapeutic strategies is discussed based on the results of mechanistic studies and the limitations associated with these therapeutic approaches.
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影响因子：
7.8
作者：
Aflaki E;Moaven N;Borger DK;Lopez G;Westbroek W;Chae JJ;Marugan J;Patnaik S;Maniwang E;Gonzalez AN;Sidransky E
通讯作者：
Sidransky E
DOI：
10.1073/pnas.2109256118
发表时间：
2021-12-28
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
12.4
作者：
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通讯作者：
Heartlein, Michael W.
DOI：
10.1073/pnas.0712309105
发表时间：
2008-02-26
影响因子：
11.1
作者：
Aerts, Johannes M.;Groener, Johanna E.;Poorthuis, Ben J.
通讯作者：
Poorthuis, Ben J.
影响因子：
10
作者：
Cabrera, Ingrid;Abasolo, Ibane;Veciana, Jaume
通讯作者：
Veciana, Jaume