Putative role of neuronal 5-lipoxygenase in an aging brain
Putative role of neuronal 5-lipoxygenase in an aging brain
复制标题
DOI：
10.1096/fj.14.10.1464
复制
发表时间：
2000-07-01
期刊：
影响因子：
4.8
通讯作者：
Qu, TY
中科院分区：
文献类型：
--
作者：
Manev, H;Uz, T;Qu, TY
衰老与神经退行性病变的发病率和/或严重程度增加有关。氧介导的事件被认为是导致神经元易感性增加的可能机制。脂氧合酶作为环氧合酶（COX），可以将氧插入花生四烯酸分子中，从而合成炎性类二十烷：白三烯[由于5-脂氧合酶（5-LOX）活性]和前列腺素（通过COX活性）。似乎5-LOX在中枢神经系统神经元中表达，并可能参与神经退行性变。5-LOX触发的细胞死亡可能由5-LOX的酶活性启动，但也可能通过5-LOX蛋白的非酶作用发生；新的数据表明5-LOX蛋白可能与酪氨酸激酶受体、细胞骨架蛋白和细胞核相互作用。神经元5-LOX的表达易受激素调控，可能是由于5-LOX基因启动子结构中存在激素响应元件。5-LOX基因的表达和5-LOX通路的活性在老年人中增加。这种5-LOX上调的一种可能机制暗示与衰老相关的激素变化有关：相对褪黑激素缺乏和/或高糖皮质激素血症。因此，5-LOX通路可能成为衰老大脑神经保护治疗的一个有希望的靶点。
Aging is associated with increased incidence and/or severity of neurodegenerative pathologies. Oxygen-mediated events are being considered as possible mechanisms responsible for the increasing neuronal vulnerability. Lipoxygenases are enzymes that, as cyclooxygenases (COX), can insert oxygen into the molecule of arachidonic acid and thereby synthesize inflammatory eicosanoids: leukotrienes [due to 5-lipoxygenase (5-LOX) activity] and prostaglandins (via COX activity), It appears that 5-LOX is expressed in central nervous system neurons and may participate in neurodegeneration. 5-LOX-triggered cell death may be initiated by the enzymatic activity of 5-LOX but could also occur via the nonenzymatic actions of the 5-LOX protein; new data point to the possibility that 5-LOX protein exerts actions such as interaction with tyrosine kinase receptors, cytoskeletal proteins, and the nucleus. The expression of neuronal 5-LOX is susceptible to hormonal regulation, presumably due to the presence of hormone-responsive elements in the structure of the 5-LOX gene promoter. The expression of the 5-LOX gene and the activity of the 5-LOX pathway are increased in elderly subjects. One possible mechanism of such 5-LOX up-regulation implies the contribution of aging-associated hormonal changes: relative melatonin deficiency and/or hyperglucocorticoidemia. Thus, the 5-LOX pathway could become a promising target of neuroprotective therapies for the aging brain.