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嗅球中组织蛋白酶的上调与实验性自身免疫性脑脊髓炎小鼠的短暂嗅觉功能障碍有关。

Upregulation of Cathepsins in Olfactory Bulbs Is Associated with Transient Olfactory Dysfunction in Mice with Experimental Autoimmune Encephalomyelitis.

机构信息

Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, 102 Jejudaehakno, Jeju, 63243, Republic of Korea.

Department of Anatomy, Kosin University College of Medicine, Busan, 49267, Republic of Korea.

出版信息

Mol Neurobiol. 2020 Aug;57(8):3412-3423. doi: 10.1007/s12035-020-01952-z. Epub 2020 Jun 11.

DOI:10.1007/s12035-020-01952-z
PMID:32529488
Abstract

Cathepsins are a family of lysosomal/endosomal proteolytic enzymes that include serine, aspartate, and cysteine proteases. The role of cathepsin in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, remains elusive. We evaluated the expression level and localization of different cathepsins in the olfactory bulbs of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Quantitative real-time PCR results and Western blotting analyses revealed that serine, aspartate, and cysteine cathepsins are expressed at significantly higher levels in the olfactory bulbs of mice with EAE in the paralytic stage compared with those of control mice. Immunohistochemical analyses indicated that cathepsin A, D, and S were expressed in the glomerulus layer, external plexiform layer, and mitral cell layer. Furthermore, cathepsins were detected in astrocytes, microglia, inflammatory cells, and vascular cells in the olfactory bulb of EAE mice at the paralytic stage. Collectively, these results suggest that the upregulation of cathepsins in the olfactory bulb of mice with EAE is associated with transient olfactory dysfunction in autoimmune encephalomyelitis.

摘要

组织蛋白酶是溶酶体/内体蛋白水解酶家族的一员,包括丝氨酸、天冬氨酸和半胱氨酸蛋白酶。组织蛋白酶在神经退行性疾病中的作用,包括阿尔茨海默病和帕金森病,仍然难以捉摸。我们评估了实验性自身免疫性脑脊髓炎(EAE)模型中嗅觉球中不同组织蛋白酶的表达水平和定位,EAE 是人类多发性硬化症的模型。实时定量 PCR 结果和 Western blot 分析显示,在麻痹阶段的 EAE 小鼠的嗅球中,丝氨酸、天冬氨酸和半胱氨酸组织蛋白酶的表达水平明显高于对照小鼠。免疫组织化学分析表明,组织蛋白酶 A、D 和 S 在肾小球层、外丛状层和僧帽细胞层表达。此外,在麻痹阶段的 EAE 小鼠嗅球中的星形胶质细胞、小胶质细胞、炎症细胞和血管细胞中检测到组织蛋白酶。总之,这些结果表明,EAE 小鼠嗅球中组织蛋白酶的上调与自身免疫性脑脊髓炎中的短暂嗅觉功能障碍有关。

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