Possible role of scavenger receptor SRCL in the clearance of amyloid-β in Alzheimer's disease.
Possible role of scavenger receptor SRCL in the clearance of amyloid-β in Alzheimer's disease.
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DOI：
10.1002/jnr.20992
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发表时间：
2006-09-01
影响因子：
4.2
通讯作者：
Nakamura, Toshikazu
中科院分区：
文献类型：
--
作者：
Nakamura, Kenji;Ohya, Wakana;Nakamura, Toshikazu
Accumulation of beta-amyloid protein (A beta) in the brain is a hallmark of Alzheimer's disease (AD), and A beta-mediated pathogenesis could result from increased production of A beta or insufficient A beta clearance by microglia, astrocytes, or the vascular system. Cell-surface receptors, such as scavenger receptors, might play a critical role in the binding and clearing of A beta; however, the responsible receptors have yet to be identified. We show that scavenger receptor with C-type lectin (SRCL), a member of the scavenger receptor family containing coiled-coil, collagen-like, and C-type lectin/carbohydrate recognition domains, is expressed in cultured astrocytes and microglia. In contrast to the low expression of SRCL in the wild-type mouse brain, in a double transgenic mouse model of AD (Tg-APP/PS1), immunohistochemistry showed that SRCL was markedly induced in A beta-positive astrocytes and A beta-positive vascular/perivascular cells, which are associated closely with cerebral amyloid angiopathy. In patients with AD, the distribution of SRCL was similar to that seen in the Tg-APP/PS1 temporal cortex. The presence of a large number of SRCL/A beta double-positive particles in the intracellular compartments of reactive astrocytes and vascular/perivascular cells in Tg-APP/PS1 mice and AD patients suggests a role for SRCL in A beta clearance. Moreover, CHO-K1 cells transfected with SRCL isoforms were found to bind fibrillar A beta(1-42). These findings suggest that SRCL could be the receptor involved in the binding or clearing of A beta by glial and vascular/perivascular cells in AD. (c) 2006 Wiley-Liss, Inc.
