Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer's-like disease progression

被引：183

作者：

Frenkel, Dan ^{[1
]}

Wilkinson, Kim ^{[2
]}

Zhao, Lingzhi ^{[2
]}

Hickman, Suzanne E. ^{[2
]}

Means, Terry K. ^{[2
]}

Puckett, Lindsay ^{[2
]}

Farfara, Dorit ^{[1
]}

Kingery, Nathan D. ^{[2
]}

Weiner, Howard L. ^{[3
]}

El Khoury, Joseph ^{[2
,4
]}

机构：

[1] Tel Aviv Univ, Dept Neurobiol, Sagol Sch Neurosci, George S Wise Fac Life Sci, IL-699788 Tel Aviv, Israel

[2] Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA

[3] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med, Boston, MA 02115 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Sch Med, Charlestown, MA 02129 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

SCAVENGER RECEPTOR; MOUSE MODEL; IN-VIVO; CD36; MICROGLIA; MACROPHAGES; OLIGOMERS; PEPTIDE; BRAINS; ROLES;

D O I：

10.1038/ncomms3030

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

In Alzheimer's disease, soluble amyloid-beta causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-beta are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-beta expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-beta in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer's disease, and generate PS1-APP-Scara1-deficient mice. Scara1 deficiency markedly accelerates A beta accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases A beta clearance. This approach is a potential treatment strategy for Alzheimer's disease.

引用

页数：9

共 40 条

[1]

Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins [J].

Borchelt, DR ;

Ratovitski, T ;

vanLare, J ;

Lee, MK ;

Gonzales, V ;

Jenkins, NA ;

Copeland, NG ;

Price, DL ;

Sisodia, SS .

NEURON, 1997, 19 (04) :939-945

[2]

CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis [J].

Bruban, Julien ;

Maoui, Agathe ;

Chalour, Naima ;

An, Na ;

Jonet, Laurent ;

Feumi, Charles ;

Treton, Jacques ;

Sennlaub, Florian ;

Behar-Cohen, Francine ;

Mascarelli, Frederic ;

Dinet, Virginie .

NEUROBIOLOGY OF DISEASE, 2011, 42 (01) :55-72

[3]

CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to β-amyloid fibrils [J].

Coraci, IS ;

Husemann, J ;

Berman, JW ;

Hulette, C ;

Dufour, JH ;

Campanella, GK ;

Luster, AD ;

Silverstein, SC ;

El Khoury, JB .

AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (01) :101-112

[4]

El Khoury J., NAT MED, V16, P1369

[5]

CD36 mediates the innate host response to β-amyloid [J].

El Khoury, JB ;

Moore, KJ ;

Means, TK ;

Leung, J ;

Terada, K ;

Toft, M ;

Freeman, MW ;

Luster, AD .

JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (12) :1657-1666

[6]

Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease [J].

El Khoury, Joseph ;

Toft, Michelle ;

Hickman, Suzanne E. ;

Means, Terry K. ;

Terada, Kinya ;

Geula, Changiz ;

Luster, Andrew D. .

NATURE MEDICINE, 2007, 13 (04) :432-438

[7]

El Khoury Joseph, 2009, MECH AMYLOID B CLEAR

[8]

ELKHOURY J, 1994, J BIOL CHEM, V269, P10197

[9]

ElKhoury J, 1996, NATURE, V382, P716

[10]

Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease [J].

Frenkel, D ;

Maron, R ;

Burt, DS ;

Weiner, HL .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (09) :2423-2433

← 1 2 3 4 →