BCL2L1 (BCL-X) promotes survival of adult and developing retinal ganglion cells
BCL2L1 (BCL-X) promotes survival of adult and developing retinal ganglion cells
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DOI：
10.1016/j.mcn.2012.07.006
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发表时间：
2012-08-01
影响因子：
3.5
通讯作者：
Libby, Richard T.
中科院分区：
文献类型：
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作者：
Harder, Jeffrey M.;Ding, Qian;Libby, Richard T.
Bcl-2 家族负责调节神经元发育期间、损伤后和疾病期间的细胞死亡途径。促死亡家族成员 BAX 的激活通常是神经元细胞死亡前的最后一步。 BCL-X (BCL2L1) 等促生存家族成员可抑制 BAX 激活。过表达研究表明 BCL-X 在调节神经元活力中发挥重要的生理作用。体内进行的功能丧失研究表明 BCL-X 在神经发育的早期阶段是神经元存活的介质。为了评估是否需要 BCL-X 来促进中枢神经系统神经元在整个生命过程中的存活，有条件地将 Bcl-x 从视杯或整个成年小鼠中去除。在发育过程中，BCL-X 是分化的视网膜神经节细胞 (RGC) 存活所必需的，直至其正常的发育死亡窗口。尽管 BCL-X 在成人 RGC 中表达，但它并不是维持成人视网膜 RGC 活力所必需的。然而，成人 RGC 中 BCL-X 的缺失确实显着增加了轴突损伤后 RGC 的死亡率。因此，在发育和受损的 RGC 中，似乎存在一个活跃的细胞生存程序来防止神经元死亡。 (C) 2012 Elsevier Inc. 保留所有权利。
The Bcl-2 family is responsible for regulating cell death pathways in neurons during development, after injury and in disease. The activation of the pro-death family member BAX is often the final step before cell death in neurons. Pro-survival family members such as BCL-X (BCL2L1) act to inhibit BAX activation. Overexpression studies have suggested that BCL-X could play an important physiological role in mediating neuronal viability. Loss-of-function studies performed in vivo have implicated BCL-X as a mediator of neuronal survival during the early stages of neurodevelopment. To assess whether BCL-X is needed to promote the survival of neurons in the central nervous system throughout life, Bcl-x was conditionally removed from the optic cup or throughout the adult mouse. During development BCL-X was required for the survival of differentiating retinal ganglion cells (RGCs) leading up to their normal window of developmental death. Despite its expression in adult RGCs, BCL-X was not required for maintaining RGC viability in adult retinas. However, the loss of BCL-X in adult RGCs did significantly increase the rate of death of RGCs after axonal injury. Thus, in developing and injured RGCs there appears to be an active cell survival program preventing neuronal death. (C) 2012 Elsevier Inc. All rights reserved.