Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr. MC0719, La Jolla, CA, 92093-0719, USA.
Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
J Mol Neurosci. 2018 Aug;65(4):420-431. doi: 10.1007/s12031-018-1110-6. Epub 2018 Jul 14.
Cathepsin protease genes are necessary for protein homeostasis in normal brain development and function. The diversity of the 15 cathepsin protease activities raises the question of what are the human brain expression profiles of the cathepsin genes during development from prenatal and infancy to childhood, adolescence, and young adult stages. This study, therefore, evaluated the cathepsin gene expression profiles in 16 human brain regions during development by quantitative RNA-sequencing data obtained from the Allen Brain Atlas resource. Total expression of all cathepsin genes was the lowest at the early prenatal stage which became increased at the infancy stage. During infancy to young adult phases, total gene expression was similar. Interestingly, the rank ordering of gene expression among the cathepsins was similar throughout the brain at the age periods examined, showing (a) high expression of cathepsins B, D, and F; (b) moderate expression of cathepsins A, L, and Z; (c) low expression of cathepsins C, H, K, O, S, and V; and (d) very low expression of cathepsins E, G, and W. Results show that the human brain utilizes well-defined, balanced patterns of cathepsin gene expression throughout the different stages of human brain development. Knowledge gained by this study of the gene expression profiles of lysosomal cathepsin proteases among human brain regions during normal development is important for advancing future investigations of how these cathepsins are dysregulated in lysosomal-related brain disorders that affect infants, children, adolescents, and young adults.
组织蛋白酶蛋白酶基因对于正常脑发育和功能的蛋白质稳态是必需的。15 种组织蛋白酶活性的多样性提出了这样一个问题，即在从产前和婴儿期到儿童期、青春期和青年期的发育过程中，人类大脑中这些组织蛋白酶基因的表达谱是什么。因此，本研究通过从 Allen 大脑图谱资源中获得的定量 RNA 测序数据，评估了 16 个人脑区域在发育过程中的组织蛋白酶基因表达谱。所有组织蛋白酶基因的总表达在早期产前阶段最低，在婴儿期增加。在婴儿期到青年期，总基因表达相似。有趣的是，在研究的年龄阶段，组织蛋白酶之间的基因表达排序在整个大脑中相似，表现出 (a) 组织蛋白酶 B、D 和 F 的高表达；(b) 组织蛋白酶 A、L 和 Z 的中等表达；(c) 组织蛋白酶 C、H、K、O、S 和 V 的低表达；和 (d) 组织蛋白酶 E、G 和 W 的极低表达。结果表明，人类大脑在不同的脑发育阶段都利用了明确的、平衡的组织蛋白酶基因表达模式。本研究对正常发育过程中人类大脑不同区域溶酶体组织蛋白酶蛋白酶基因表达谱的研究结果，对于推进这些组织蛋白酶在影响婴儿、儿童、青少年和青年的溶酶体相关脑疾病中失调的未来研究具有重要意义。
