Familian Atoosa, Eikelenboom Piet, Veerhuis Robert
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
Neurosci Lett. 2007 Apr 6;416(1):87-91. doi: 10.1016/j.neulet.2007.01.052. Epub 2007 Jan 27.
Activated microglia accumulate in amyloid beta (Abeta) plaques containing amyloid associated factors SAP and C1q in Alzheimer's disease (AD) brain. Microglia are involved in AD pathogenesis by promoting Abeta plaque formation and production of pro-inflammatory cytokines. On the other hand, phagocytosis of Abeta by activated microglia may prevent Abeta-mediated neurotoxicity and Abeta plaque formation. Minocycline, a tetracycline derivative, is neuroprotective in various neurodegenerative models as well as human chronic neurological disorders. Minocycline attenuates the release of TNF-alpha by human microglia upon exposure to a mixture of Abeta, SAP and C1q. Here, we demonstrate that minocycline down-regulates the production of pro-inflammatory cytokines by human microglia without affecting their beneficial activity, phagocytosis of amyloid beta fibrils.
在阿尔茨海默病（AD）大脑中，活化的小胶质细胞聚集在含有淀粉样蛋白相关因子SAP和C1q的淀粉样β（Aβ）斑块中。小胶质细胞通过促进Aβ斑块形成和促炎细胞因子的产生参与AD发病机制。另一方面，活化的小胶质细胞对Aβ的吞噬作用可能会预防Aβ介导的神经毒性和Aβ斑块形成。米诺环素是一种四环素衍生物，在各种神经退行性模型以及人类慢性神经疾病中具有神经保护作用。当暴露于Aβ、SAP和C1q的混合物时，米诺环素可减弱人小胶质细胞释放肿瘤坏死因子-α（TNF-α）。在此，我们证明米诺环素可下调人小胶质细胞促炎细胞因子的产生，而不影响其有益活性，即对淀粉样β纤维的吞噬作用。
