Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
J Alzheimers Dis. 2010;22(1):97-105. doi: 10.3233/JAD-2010-100261.
Deposition of amyloid-β peptide (Aβ) and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Recently, calcineurin (CaN) has been reported as a potential modulator of memory function, synaptic plasticity, and neural degeneration in brains of AD animal models. In the present study, we examined the relationship between Aβ accumulations and CaN activity in brains of the AβPP/PS1 double transgenic mice. Treatment with FK506, a CaN inhibitor, significantly reduces Aβ burden and restores synaptic proteins (synaptophysin and postsynaptic density protein-95; PSD-95) while inducing matrix metallopeptidase-9 (MMP-9) expression in GFAP-positive astrocytes in the brain. These results suggest a role of FK506 and control of CaN activity in neuroprotection associated with Aβ deposition in AD.
淀粉样β肽 (Aβ) 的沉积和神经纤维缠结是阿尔茨海默病 (AD) 的病理学标志，AD 是一种以认知缺陷和神经元丧失为特征的神经退行性疾病。最近，钙调神经磷酸酶 (CaN) 被报道为 AD 动物模型大脑中记忆功能、突触可塑性和神经退行性变的潜在调节剂。在本研究中，我们研究了 AβPP/PS1 双转基因小鼠大脑中 Aβ 积累与 CaN 活性之间的关系。FK506（一种 CaN 抑制剂）的治疗显著降低了 Aβ 负担，并恢复了突触蛋白（突触小体蛋白和突触后密度蛋白-95；PSD-95），同时诱导 GFAP 阳性星形胶质细胞中基质金属蛋白酶-9 (MMP-9) 的表达。这些结果表明 FK506 的作用和 CaN 活性的控制在与 AD 中 Aβ 沉积相关的神经保护中起作用。
