Effective Targeting of A尾 to Macrophages by Sonochemically Prepared Surface-Modified Protein Microspheres

详细信息    查看全文

• 作者：Michal Richman ; Alex Perelman ; Asaf Gertler ; Shai Rahimipour
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：January 14, 2013
• 年：2013
• 卷：14
• 期：1
• 页码：110-116
• 全文大小：404K
• 年卷期：v.14,no.1(January 14, 2013)
• ISSN：1526-4602

文摘

Imbalanced homeostasis and oligomerization of the amyloid-尾 (A尾) peptide in the brain are hallmarks of Alzheimer鈥檚 disease (AD). Microglia and macrophages play a critical role in the etiology of AD either by clearing A尾 from the brain or inducing inflammation. Recent evidence suggests that clearance of A尾 by microglia/macrophages via the phagocytic pathway is defective in AD, which can contribute to the accumulation of A尾 in the brain. We have recently demonstrated that protein microspheres modified at their surface with multiple copies of an A尾-recognition motif can strongly bind A尾, inhibit its aggregation, and directly reduce its toxicity by sequestering it from the medium. Here, we describe how microsphere-bound A尾 can stimulate microglial cells and be phagocytosed through a mechanism that is distinct from that of A尾 removal and, thus, contribute to the clearance of A尾, even by defective microglial cells. The phagocytosis was most effective, with microspheres having a diameter of <1 渭m. The introduction of polyethylene glycol to the surface of the microspheres changed the kinetics of the phagocytosis. Moreover, while aggregated A尾 induced a significant inflammatory response that was manifested by the release of TNF-伪, the microsphere-bound A尾 dramatically reduced the amount of cytokine released from microglial cells.