The Role of AMPK Pathway in Neuroprotection.
The Role of AMPK Pathway in Neuroprotection.
复制标题
AMPK 通路在神经保护中的作用。
DOI：
10.1007/978-3-319-17121-0_56
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发表时间：
2016
影响因子：
--
通讯作者：
Ash,JohnD
中科院分区：
文献类型：
--
作者：
Xu,Lei;Ash,JohnD
腺苷单磷酸活化激酶（AMPK）是一种高度保守的蛋白激酶，存在于所有真核生物基因组中。它以异源三聚体蛋白的形式存在，由α、β和γ亚基组成。AMPK被升高的单磷酸腺苷（AMP）激活，AMP是在低ATP产生和可能线粒体功能障碍的条件下产生的。AMPK的激活已被证明可以调节大量的下游通路。它们要么会增加能量产生，如增加脂肪酸和葡萄糖的氧化，要么会减少能量利用，如抑制糖原合成、脂肪酸合成和蛋白质合成。此外，作为生理能量动力学的关键调节因子，AMPK已被证明在调节线粒体生物发生等各种细胞过程中发挥作用（Jager等）。中国生物医学工程学报，34(4):1107 - 1107,2007)，自噬（Hyttinen等）。Rejuven Res 14:651-660, 2011)和炎症和免疫反应（Giri et al. 2004）。视网膜神经元能量需求高，但能量储存能力差。因此，AMPK信号通路可能在维持能量平衡中发挥重要作用，因此可能是预防或延缓视网膜变性的治疗靶点。
Adenosine monophosphate-activated kinase (AMPK) is a highly conserved protein kinase found in all eukaryotic genomes. It exists as heterotrimeric protein consisting of α, β, and γ subunits. AMPK is activated by elevated levels of adenosine mono-phosphate (AMP), which is produced during conditions of low ATP production and perhaps mitochondrial dysfunction. Activation of AMPK has been shown to regulate a large number of downstream pathways. These will either increase energy production such as increase oxidation of fatty acids and glucose, or decrease energy utilization such as inhibiting synthesis of glycogen, fatty acid synthesis, and protein synthesis. In addition, being a key regulator of physiological energy dynamics, AMPK has been demonstrated to play roles in regulating various cellular processes such as mitochondrial biogenesis (Jager et al. Proc Natl Acad Sci U S A 104:12017–12022, 2007), autophagy (Hyttinen et al. Rejuven Res 14:651–660, 2011) and inflammation and immune responses (Giri et al. 2004). Retinal neurons have a high energy demand but have a poor energy storage capacity. Because of this, it is likely that the AMPK signaling pathway plays an important role in maintaining energy balance, and therefore may be a therapeutic target to prevent or delay retinal degeneration.