Facilitation of brain mitochondrial activity by 5-aminolevulinic acid in a mouse model of Alzheimer's disease
Facilitation of brain mitochondrial activity by 5-aminolevulinic acid in a mouse model of Alzheimer's disease
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DOI：
10.1080/1028415x.2016.1199114
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发表时间：
2017-01-01
影响因子：
3.6
通讯作者：
Hata, Saori
中科院分区：
文献类型：
--
作者：
Omori, Chiori;Motodate, Rika;Hata, Saori
线粒体酶的活性对神经功能至关重要，随着年龄的增长和与年龄相关的疾病，线粒体的活性会下降。尤其是阿尔茨海默病(AD)患者细胞色素c氧化酶(COX/Complex IV)活性降低。环氧合酶是一种含有血红素的线粒体内膜蛋白复合体，在产生三磷酸腺苷的电子传递链中起着至关重要的作用。血红素的合成始于线粒体中的5-氨基乙酰丙酸(5-ALA)。5-丙氨酸合成酶是血红素合成的限速酶，提示补充5-丙氨酸可能有助于保护老年脑中线粒体的活性。我们给三转基因AD(3xTg-AD)模型小鼠喂食含5-ALA的食物6个月，从3个月大开始。饲喂5-ALA的小鼠脑内COX活性和蛋白表达以及线粒体膜电位显著高于对照组。在喂食5-ALA的小鼠中，突触聚集蛋白水平也显著更高，这表明突触的保存得到了改善。尽管5-ALA喂养的小鼠脑A水平有下降趋势，但我们没有观察到AD的其他生化和病理特征的显著变化。然而，我们的研究表明，每天口服5-ALA可以保存老年人大脑中的线粒体酶活性，从而有助于保存神经活动。
The activities of mitochondrial enzymes, which are essential for neural function, decline with age and in age-related disease. In particular, the activity of cytochrome c oxidase (COX/complex IV) decreases in patients with Alzheimer's disease (AD). COX, a mitochondrial inner membrane protein complex that contains heme, plays an essential role in the electron transport chain that generates ATP. Heme synthesis begins with 5-aminolevulinic acid (5-ALA) in mitochondria. 5-ALA synthetase is the rate-limiting enzyme in heme synthesis, suggesting that supplementation with 5-ALA might help preserve mitochondrial activity in the aged brain. We administered a diet containing 5-ALA to triple-transgenic AD (3xTg-AD) model mice for 6 months, starting at 3 months of age. COX activity and protein expression, as well as mitochondrial membrane potential, were significantly higher in brains of 5-ALA-fed mice than in controls. Synaptotagmin protein levels were also significantly higher in 5-ALA-fed mice, suggesting improved preservation of synapses. Although brain A levels tended to decrease in 5-ALA-fed mice, we observed no other significant changes in other biochemical and pathological hallmarks of AD. Nevertheless, our study suggests that daily oral administration of 5-ALA could preserve mitochondrial enzyme activities in the brains of aged individuals, thereby contributing to the preservation of neural activity.