Heme catabolism and heme oxygenase in neurodegenerative disease.
Heme catabolism and heme oxygenase in neurodegenerative disease.
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DOI：
10.1089/ars.2004.6.888
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发表时间：
2004-10
影响因子：
6.6
通讯作者：
A. Takeda;Y. Itoyama;T. Kimpara;Xiongwei Zhu;J. Ávila;B. Dwyer;George Perry;Mark A. Smith
中科院分区：
文献类型：
--
作者：
A. Takeda;Y. Itoyama;T. Kimpara;Xiongwei Zhu;J. Ávila;B. Dwyer;George Perry;Mark A. Smith
血红素加氧酶是血红素分解代谢的限速步骤，似乎在许多神经退行性疾病（例如阿尔茨海默病）中发挥着重要作用。有趣的是，患病大脑中血红素加氧酶-1 表达的空间分布与 tau 病理表达的空间分布基本相同，表明两者在疾病进展中都发挥着关键作用。与血红素加氧酶一样，tau 蛋白的表达、磷酸化和聚集通过信号级联进行调节，包括细胞外信号调节激酶，其活性受氧化应激调节。因此，tau 和血红素加氧酶-1 的协调表达可能在神经元细胞的细胞保护中发挥关键作用。这将血红素加氧酶置于疾病发病机制的中心，并提供了一种针对酶诱导的原因或后果的新型治疗方法。
Heme oxygenase, the rate-limiting step in heme catabolism, appears to play an important role in a number of neurodegenerative disorders, such as Alzheimer disease. Interestingly, the spatial distribution of heme oxygenase-1 expression in diseased brain is essentially identical to that of the pathological expression of tau, suggesting a key role for both in disease progression. Like heme oxygenase, the expression, phosphorylation, and aggregation of tau are regulated through signal cascades, including the extracellular signal-regulated kinases, whose activities are modulated by oxidative stress. Therefore, the expression of tau and heme oxygenase-1 in a coordinated manner likely plays a pivotal role in the cytoprotection of neuronal cells. This places heme oxygenase at the center of disease pathogenesis and offers a novel therapeutic approach targeted at either the causes or consequences of enzyme induction.