Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid β-induced memory impairment
Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid β-induced memory impairment
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DOI：
10.1016/j.bbr.2014.03.046
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发表时间：
2014-07-15
影响因子：
2.7
通讯作者：
Suzumura, Akio
中科院分区：
文献类型：
--
作者：
Fukumoto, Kazuya;Mizoguchi, Hiroyuki;Suzumura, Akio
阿尔茨海默病是一种进行性神经退行性疾病。淀粉样β蛋白是一种神经毒性蛋白，会导致海马区突触可塑性的破坏，并导致阿尔茨海默病患者的认知障碍。我们之前。研究发现，一种用于治疗多发性硬化症的新型口服免疫抑制剂Fingolimod通过上调神经元脑源性神经营养因子(BDNF)的表达，改善了寡聚淀粉样β蛋白诱导的神经元损伤。在这里，我们发现口服Fingolimod改善了注射淀粉样β蛋白的小鼠在目标识别、记忆和联想学习方面的损害。这一效应与大脑皮层和海马区BDNF正常表达水平的恢复有关，表明神经保护是通过上调神经元BDNF水平而介导的。因此，Fingolimod可能为阿尔茨海默病患者提供治疗效果。(C)2014爱思唯尔B.V.保留所有权利。
Alzheimer's disease is a progressive neurodegenerative disorder. Amyloid beta, a neurotoxic protein, causes disruption of hippocampal synaptic plasticity, and induces cognitive impairment in Alzheimer's disease. We previously. revealed that fingolimod, a new oral immunosuppressant used to treat multiple sclerosis, ameliorates oligomeric amyloid beta-induced neuronal damage via up-regulation of neuronal brain-derived neurotrophic factor (BDNF). Here, we showed that oral administration of fingolimod ameliorated the impairment in object recognition memory and associative learning in mice injected with amyloid beta. This effect was associated with restoration of normal BDNF expression levels in the cerebral cortices and hippocampi, suggesting that neuroprotection was mediated by up-regulation of neuronal BDNF levels. Therefore, fingolimod may provide therapeutic effects in patients with Alzheimer's disease. (C) 2014 Elsevier B.V. All rights reserved.