title: Inhibition of cathepsin S produces neuroprotective effects after traumatic brain injury in mice.
abstract: Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic pain. In this study, we investigated the time course of CatS protein and mRNA expression and the cellular distribution of CatS in a mouse model of traumatic brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor, and examined the effect on inflammation and neurobehavioral function. We found that expression of CatS was increased as early as 1 h after TBI at both protein and mRNA levels. The increased expression was detected in microglia and neurons. Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema. Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function. These results imply that CatS is involved in the secondary injury after TBI and provide a new perspective for preventing secondary injury after TBI.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.forename: Xinyu
authors.initials: X
authors.lastname: Lu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wang
authors.forename: Chunxi
authors.initials: C
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology*; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003593:Cytoplasm / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D004487:Edema / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004151:Dipeptides; C532594:N-morpholinourea-leucine-homophenylalanine-phenyl-vinylsulfone; D018696:Neuroprotective Agents; D013450:Sulfones; D002403:Cathepsins; C028217:cathepsin S