脑腱黄瘤病的发病机制与药物治疗。
The pathogenesis of, and pharmacological treatment for, Canavan disease.
机构信息
Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Baltimore, MD 21205, USA.
Department of Anatomy, Physiology and Genetics and Neuroscience Program, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
出版信息
Drug Discov Today. 2022 Sep;27(9):2467-2483. doi: 10.1016/j.drudis.2022.05.019. Epub 2022 May 27.
Abstract
Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the gene encoding aspartoacylase (ASPA). ASPA is highly expressed in oligodendrocytes and catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate. In this review, we examine the pathologies and clinical presentation in CD, the metabolism and transportation of NAA in the brain, and the hypothetical mechanisms whereby ASPA deficiency results in dysmyelination and a failure of normal brain development. We also discuss therapeutic options that could be used for the treatment of CD.
摘要
Canavan 病（CD）是一种遗传性脑白质营养不良，由编码天冬氨酸酰基酶（ASPA）的基因突变引起。ASPA 在少突胶质细胞中高度表达，并催化 N-乙酰天冬氨酸（NAA）的裂解，生成天冬氨酸和乙酸盐。在这篇综述中，我们研究了 CD 的病理学和临床表现、脑内 NAA 的代谢和转运，以及 ASPA 缺乏导致脱髓鞘和正常大脑发育失败的假设机制。我们还讨论了可用于治疗 CD 的治疗选择。
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