期刊论文详细信息
FEBS Letters
Effect of chloroquine and leupeptin on intracellular accumulation of amyloid‐beta (Aβ) 1–42 peptide in a murine N9 microglial cell line
Yang, Fusheng2  Tran, Thuy2  Chu, Teresa2  Frautschy, Sally A2  Beech, Walter1  Cole, Greg M2 
[1] Geriatric Research Education and Clinical Center, Sepulveda VAMC, 16111 Plummer Street, Sepulveda, CA 91343, USA;Department of Medicine, University of California, Los Angeles, USA
关键词: Alzheimer's disease;    βA4 amyloid;    Lysosome;    Microglia;    Chloroquine;    Leupeptin;   
DOI  :  10.1016/S0014-5793(98)01161-2
学科分类:生物化学/生物物理
来源: John Wiley & Sons Ltd.
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【 摘 要 】

Murine N9 microglia accumulated Aβ from media containing 0.67 μM Aβ within 6 h. In N9 and in primary rat microglia, chloroquine, which disrupts lysosomal pH, increased Aβ-induced accumulation of Aβ, particularly Aβ1–42. Leupeptin similarly enhanced Aβ accumulation. The scavenger receptor antagonist fucoidan did not affect acute chloroquine-dependent Aβ1–42 accumulation, demonstrating uptake of non-aggregated Aβ. After prolonged incubations, chloroquine enhanced Aβ multimer (8–12 kDa) accumulation, an effect inhibited by fucoidan. Disruptions of the lysosomal system enhance Aβ and its multimer formation. Despite negligible effects of fucoidan on initial Aβ uptake, chronic exposure inhibits multimer accumulation, demonstrating a role for scavenger receptor in multimer accumulation.

【 授权许可】

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