FOXO in Neural Cells and Diseases of the Nervous System.
FOXO in Neural Cells and Diseases of the Nervous System.
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DOI：
10.1016/bs.ctdb.2017.10.002
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发表时间：
2018
影响因子：
--
通讯作者：
Paik J
中科院分区：
文献类型：
--
作者：
Santo EE;Paik J
进化上保守的FOXO家族转录因子已成为神经细胞命运和功能的重要仲裁者。从神经干细胞状态到生理和病理条件下的成熟神经元，已经发现它们调节神经细胞存活、应激反应、谱系定型和神经元信号传导。谱系特异性FOXO敲除小鼠为解剖神经系统中的FOXO生物学提供了宝贵的工具。在脑的神经干细胞区室中，需要FOXO来维持NSC静止和清除活性氧。在成熟神经元内，FOXO转录活性对于防止年龄依赖性轴突变性是必不可少的。急性，FOXO 3已被发现在神经营养因子撤出后引起轴突变性。在更活跃的神经信号中，FOXO 6促进海马神经元树突棘密度的增加，并且是巩固记忆所必需的。除了中枢神经系统（CNS）外，FOXO还影响周围神经系统（PNS）的功能。PNS内的FOXO 1敲除导致交感神经张力降低和脑源性去甲肾上腺素水平降低以及能量消耗降低。FOXO 3基因敲除小鼠的听力受损可能是由于耳内突触定位缺陷所致。考虑到FOXO在CNS和PNS中的活性范围，在神经退行性疾病如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩性侧索硬化症的背景下研究FOXO将是有意义的。在神经系统内，FOXO也可以调节重要的参数，如全身代谢，运动功能和儿茶酚胺的产生;使FOXO在生理稳态中发挥关键作用。
The evolutionarily-conserved FOXO family of transcription factors has emerged as a significant arbiter of neural cell fate and function. From the neural stem cell state through mature neurons under both physiological and pathological conditions they have been found to modulate neural cell survival, stress responses, lineage commitment and neuronal signaling. Lineage-specific FOXO knockout mice have provided an invaluable tool for the dissection of FOXO biology in the nervous system. Within the neural stem cell compartments of the brain FOXOs are required for the maintenance of NSC quiescence and for the clearance of reactive oxygen species. Within mature neurons FOXO transcriptional activity is essential for the prevention of age-dependent axonal degeneration. Acutely, FOXO3 has been found to cause axonal degeneration upon withdrawal of neurotrophic factors. In more active neural signaling, FOXO6 promotes increased dendritic spine density of hippocampal neurons and is required for the consolidation of memories. In addition to the central nervous system (CNS) FOXOs also influence the functionality of the peripheral nervous system (PNS). FOXO1 knockout within the PNS results in a reduction of sympathetic tone and decreased levels of brain-derived norepinephrine and lower energy expenditure. FOXO3 knockout mice have impaired hearing which may be due to defects in synapse localization within the ear. Given the scope of FOXO activities in both the CNS and PNS it will be of interest to study FOXOs within the context of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Amyotrophic Lateral Sclerosis. From within the nervous system FOXOs may also regulate important parameters such as whole-body metabolism, motor function and catecholamine production; making FOXOs key players in physiologic homeostasis.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.5
作者：
Dumitriu A;Latourelle JC;Hadzi TC;Pankratz N;Garza D;Miller JP;Vance JM;Foroud T;Beach TG;Myers RH
通讯作者：
Myers RH
影响因子：
25
作者：
通讯作者：
--
FOXO转录因子直接激活BIM基因表达并促进交感神经元中的凋亡。
影响因子：
7.8
作者：
Gilley, Jonathan;Coffer, Paul J;Ham, Jonathan
通讯作者：
Ham, Jonathan
影响因子：
3.7
作者：
de Candia P;Blekhman R;Chabot AE;Oshlack A;Gilad Y
通讯作者：
Gilad Y