Takeda Atsushi, Itoyama Yasuto, Kimpara Teiko, Zhu Xiongwei, Avila Jesús, Dwyer Barney E, Perry George, Smith Mark A
Department of Neurology, Tohoku University School of Medicine, Sendai 980-8574, Japan.
Antioxid Redox Signal. 2004 Oct;6(5):888-94. doi: 10.1089/ars.2004.6.888.
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.
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（如阿尔茨海默病）中发挥重要作用。有趣的是，血红素加氧酶-1在患病大脑中的空间分布与tau蛋白的病理表达基本相同，这表明二者在疾病进展中都起着关键作用。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反应进行调节，包括细胞外信号调节激酶，其活性受氧化应激调节。因此，tau蛋白和血红素加氧酶-1的协同表达可能在神经元细胞的细胞保护中起关键作用。这使得血红素加氧酶处于疾病发病机制的中心位置，并提供了一种针对酶诱导的原因或后果的新型治疗方法。
