Cystatin C inhibits amyloid-β deposition in Alzheimer's disease mouse models

被引：165

作者：

Mi, Weiqian

Pawlik, Monika

Sastre, Magdalena

Jung, Sonia S.

Radvinsky, David S.

Klein, Andrew M.

Sommer, John

Schmidt, Stephen D.

Nixon, Ralph A.

Mathews, Paul M.

Levy, Efrat ^{[1
]}

机构：

[1] Nathan S Kline Inst, Orangeburg, NY 10962 USA

[2] NYU, Sch Med, New York, NY 10016 USA

[3] Centocor Res & Dev Inc, Radnor, PA 19087 USA

来源：

NATURE GENETICS | 2007年 / 39卷 / 12期

关键词：

D O I：

10.1038/ng.2007.29

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Using transgenic mice expressing human cystatin C ( encoded by CST3), we show that cystatin C binds soluble amyloid-beta peptide and inhibits cerebral amyloid deposition in amyloid-beta precursor protein ( APP) transgenic mice. Cystatin C expression twice that of the endogenous mouse cystatin C was sufficient to substantially diminish amyloid-beta deposition. Thus, cystatin C has a protective role in Alzheimer's disease pathogenesis, and modulation of cystatin C concentrations may have therapeutic implications for the disease.

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收藏

页码：1440 / 1442

页数：3

相关论文

共 15 条

[1] Alzheimer disease-associated cystatin C variant undergoes impaired secretion [J].

Benussi, L ;

Ghidoni, R ;

Steinhoff, T ;

Alberici, AA ;

Villa, A ;

Mazzoli, F ;

Nicosia, F ;

Barbiero, L ;

Broglio, L ;

Feudatari, E ;

Signorini, S ;

Finckh, U ;

Nitsch, RM ;

Binetti, G .

NEUROBIOLOGY OF DISEASE, 2003, 13 (01) :15-21

[2] Presenilin 2 mutations alter cystatin C trafficking in mouse primary neurons [J].

Ghidoni, Roberta ;

Benussi, Luisa ;

Paterlini, Anna ;

Missale, Cristina ;

Usardi, Alessia ;

Rossi, Rossana ;

Barbiero, Laura ;

Spano, PierFranco ;

Binetti, Giuliano .

NEUROBIOLOGY OF AGING, 2007, 28 (03) :371-376

[3] HEREDITARY CEREBRAL HEMORRHAGE WITH AMYLOIDOSIS [J].

GUDMUNDSSON, G ;

HALLGRIMSSON, J ;

BJARNASON, O ;

JONASSON, TA .

BRAIN, 1972, 95 :387-+

[4] Correlative memory deficits, A beta elevation, and amyloid plaques in transgenic mice [J].

Hsiao, K ;

Chapman, P ;

Nilsen, S ;

Eckman, C ;

Harigaya, Y ;

Younkin, S ;

Yang, FS ;

Cole, G .

SCIENCE, 1996, 274 (5284) :99-102

[5] CEREBRAL AMYLOID ANGIOPATHY - A SIGNIFICANT CAUSE OF CEREBELLAR AS WELL AS LOBAR CEREBRAL-HEMORRHAGE IN THE ELDERLY [J].

ITOH, Y ;

YAMADA, M ;

HAYAKAWA, M ;

OTOMO, E ;

MIYATAKE, T .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 1993, 116 (02) :135-141

[6] The role of cystatin C in cerebral amyloid angiopathy and stroke: Cell biology and animal models [J].

Levy, E ;

Jaskolski, M ;

Grubb, A .

BRAIN PATHOLOGY, 2006, 16 (01) :60-70

[7] STROKE IN ICELANDIC PATIENTS WITH HEREDITARY AMYLOID ANGIOPATHY IS RELATED TO A MUTATION IN THE CYSTATIN-C GENE, AN INHIBITOR OF CYSTEINE PROTEASES [J].

LEVY, E ;

LOPEZOTIN, C ;

GHISO, J ;

GELTNER, D ;

FRANGIONE, B .

JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 169 (05) :1771-1778

[8] Codeposition of cystatin C with amyloid-β protein in the brain of Alzheimer disease patients [J].

Levy, E ;

Sastre, M ;

Kumar, A ;

Gallo, G ;

Piccardo, P ;

Ghetti, B ;

Tagliavini, F .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2001, 60 (01) :94-104

[9] Serum cystatin C as a marker of glomerular filtration rate [J].

Madero, Magdalena ;

Sarnak, Mark J. ;

Stevens, Lesley A. .

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 2006, 15 (06) :610-616

[10] IMMUNOHISTOCHEMICAL CHARACTERIZATION OF CEREBROVASCULAR AMYLOID IN 46 AUTOPSIED CASES USING ANTIBODIES TO BETA-PROTEIN AND CYSTATIN-C [J].

MARUYAMA, K ;

IKEDA, SI ;

ISHIHARA, T ;

ALLSOP, D ;

YANAGISAWA, N .

STROKE, 1990, 21 (03) :397-403