The α-Ketoglutarate Dehydrogenase Complex as a Hub of Plasticity in Neurodegeneration and Regeneration.
The α-Ketoglutarate Dehydrogenase Complex as a Hub of Plasticity in Neurodegeneration and Regeneration.
复制标题
DOI：
10.3390/ijms232012403
复制
发表时间：
2022-10-17
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
葡萄糖代谢异常是神经退行性变的核心，大量证据表明三羧酸（TCA）循环关键酶的异常是代谢缺陷的基础。近期在代谢在癌症中作用方面的重大进展提供了新的见解，有助于我们理解代谢在神经退行性变中的作用。研究表明，TCA循环的限速步骤——α - 酮戊二酸脱氢酶复合物（KGDHC）及其底物α - 酮戊二酸（KG），作为一个信号枢纽调节多种细胞过程：（1）是TCA循环的限速步骤；（2）对活性氧（ROS）敏感并产生ROS；（3）决定KG是用于能量还是用于合成支持生长的化合物；（4）调节细胞对缺氧的反应；（5）通过琥珀酰化调节线粒体、细胞质和细胞核中数百种细胞蛋白质的翻译后修饰；（6）控制转录的关键方面；（7）调节细胞内的蛋白质信号传导；（8）调节细胞内钙。本综述的主要重点是了解KGDHC的减少如何转化为对神经退行性变和癌症都至关重要的病理变化。了解每一种作用对于开发治疗神经退行性疾病的新治疗策略是必要的。
Abnormal glucose metabolism is central to neurodegeneration, and considerable evidence suggests that abnormalities in key enzymes of the tricarboxylic acid (TCA) cycle underlie the metabolic deficits. Significant recent advances in the role of metabolism in cancer provide new insight that facilitates our understanding of the role of metabolism in neurodegeneration. Research indicates that the rate-limiting step of the TCA cycle, the α-ketoglutarate dehydrogenase complex (KGDHC) and its substrate alpha ketoglutarate (KG), serve as a signaling hub that regulates multiple cellular processes: (1) is the rate-limiting step of the TCA cycle, (2) is sensitive to reactive oxygen species (ROS) and produces ROS, (3) determines whether KG is used for energy or synthesis of compounds to support growth, (4) regulates the cellular responses to hypoxia, (5) controls the post-translational modification of hundreds of cell proteins in the mitochondria, cytosol, and nucleus through succinylation, (6) controls critical aspects of transcription, (7) modulates protein signaling within cells, and (8) modulates cellular calcium. The primary focus of this review is to understand how reductions in KGDHC are translated to pathologically important changes that underlie both neurodegeneration and cancer. An understanding of each role is necessary to develop new therapeutic strategies to treat neurodegenerative disease.
登录
查看更多内容
影响因子：
4.7
作者：
Ambrus, Attila;Tretter, Laszlo;Adam-Vizi, Vera
通讯作者：
Adam-Vizi, Vera
DOI：
10.1097/00005072-199909000-00005
发表时间：
1999-09-01
影响因子：
3.2
作者：
Calingasan, NY;Chun, WJ;Gibson, GE
通讯作者：
Gibson, GE
影响因子：
6
作者：
Calingasan, NY;Park, LCH;Gibson, GE
通讯作者：
Gibson, GE
影响因子：
2.5
作者：
CALINGASAN, NY;BAKER, H;GIBSON, GE
通讯作者：
GIBSON, GE
影响因子：
4.7
作者：
Chen, Huanlian;Cross, Abigail C.;Gibson, Gary E.
通讯作者：
Gibson, Gary E.