Qu Baoxi, Gong Yunhua, Gill Jassica M, Kenney Kimbra, Diaz-Arrastia Ramon
Center for Neuroscience and Regenerative Medicine, Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Center for Neuroscience and Regenerative Medicine, Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Brain Res. 2017 Sep 1;1670:248-252. doi: 10.1016/j.brainres.2017.06.021. Epub 2017 Jun 23.
Cytosolic phospholipase A2α (cPLA2α) is a key enzyme in regulation of inflammation process and neuromembrane homeostasis, both of which are critical in pathogenesis of Alzheimer's diseases. By hybride APP/PS1 Tg-AD mice with cPLA2α knockout mice, three lines of APP/PS1 Tg-AD mice were produced with genotypes of cPLA2α, cPLA2α and cPLA2α. Compared to cPLA2α Tg-AD mice, the amyloid plaque formation was significantly downregulated in the brain of cPLA2α Tg-AD mice, but not in cPLA2α Tg-AD mice. The reactive gliosis were also significantly downregulated in both cPLA2α and cPLA2α Tg-AD mouse lines. The paradoxical effects of cPLA2α on the amyloid plaques reveal a complex role of cPLA2α in pathogenesis of AD and could be a potential target for prevention and treatment of AD.
胞质型磷脂酶A2α（cPLA2α）是炎症过程调节和神经膜稳态中的关键酶，这两者在阿尔茨海默病的发病机制中都至关重要。通过将APP/PS1转基因阿尔茨海默病（Tg-AD）小鼠与cPLA2α基因敲除小鼠杂交，产生了三系APP/PS1 Tg-AD小鼠，其基因型分别为cPLA2α、cPLA2α和cPLA2α。与cPLA2α转基因阿尔茨海默病小鼠相比，cPLA2α转基因阿尔茨海默病小鼠大脑中的淀粉样斑块形成显著下调，但cPLA2α转基因阿尔茨海默病小鼠中未出现这种情况。在cPLA2α和cPLA2α转基因阿尔茨海默病小鼠品系中，反应性胶质增生也显著下调。cPLA2α对淀粉样斑块的矛盾作用揭示了cPLA2α在阿尔茨海默病发病机制中的复杂作用，并且可能成为阿尔茨海默病预防和治疗的潜在靶点。
