Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies

	Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies
	Xu, L; Sheng, JS; Tang, ZS; Wu, XF; Yu, Y; Guo, H; Shen, Y; Zhou, CF; Paraoan, L; Zhou, JW
刊名	NEUROBIOLOGY OF DISEASE
	2005
卷号	18 期号:1 页码:152-165
关键词	cystatin C dopaminergic cathepsin Parkinson's disease cell culture
通讯作者	Zhou, JW (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Key Lab Proteom, Bldg 23,Room 316,320 Yueyang Rd, Shanghai 200031, Peoples R China.,jwzhou@sibs.ac.cn
英文摘要	Destruction of nigrostriatal dopaminergic (DA) pathway triggers various persistent responses, such as inflammation and increased synthesis of neural growth factors, both in striatum and in substantia nigra. The pathological processes involved in such responses are poorly characterized and could contribute to secondary damage and/or regeneration in the central nervous system (CNS). Cystatin C was previously implicated in the process of neurodegeneration. However, its biological role during neurodegeneration is not understood and remains controversial. The present study identified an increased cystatin C mRNA level in the DA-depleted rat striatum, starting from the second week following a 6-OHDA-induced lesion. Immunohistochemical analysis confirmed the increase in cystatin C protein level in the striatum following DA depletion. Double-labeled fluorescence immunohistochemical istry revealed that nigrostriatal neurons, astrocytes, and microglia contributed to the elevated level of cystatin C. Exposure to 6-hydroxydopamine, a DA-specific neurotoxin, resulted in DA neurons loss in the fetal mesencephalic cultures, an effect which could be partially reversed by treatment with cystatin C. Moreover, in vivo DA neurons survival study showed that administration of cystatin C in rats with 6-OHDA-induced lesion partially rescued the nigral DA neurons. The results indicate that the 6-OHDA lesioning induced a relatively slow but sustained up-regulation of cystatin C expression and suggest that the inhibitor may exert a neuroprotective action on DA neurons. The findings raise the possibility that cysteine proteinase inhibitors may be new candidates for neuroprotective treatment of Parkinson's disease. Cystatin C may be useful therapeutically in limiting neuropathy in Parkinson's disease. (C) 2004 Elsevier Inc. All rights reserved.
学科主题	Neurosciences & Neurology
类目[WOS]	Neurosciences
关键词[WOS]	CYSTEINE PROTEINASE-INHIBITORS ; TUMOR-NECROSIS-FACTOR ; PARKINSONS-DISEASE ; 6-HYDROXYDOPAMINE LESIONS ; CATHEPSIN-B ; GAMMA-TRACE ; MESSENGER-RNA ; NIGROSTRIATAL PATHWAY ; HIPPOCAMPAL-NEURONS ; CEREBROSPINAL-FLUID
收录类别	SCI
语种	英语
WOS记录号	WOS:000226452500015
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1843]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Xu, L,Sheng, JS,Tang, ZS,et al. Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies[J]. NEUROBIOLOGY OF DISEASE,2005,18(1):152-165.
APA	Xu, L.,Sheng, JS.,Tang, ZS.,Wu, XF.,Yu, Y.,...&Zhou, JW.(2005).Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies.NEUROBIOLOGY OF DISEASE,18(1),152-165.
MLA	Xu, L,et al."Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies".NEUROBIOLOGY OF DISEASE 18.1(2005):152-165.