Retinoic acid signaling in axonal regeneration
Retinoic acid signaling in axonal regeneration
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DOI：
10.3389/fnmo1.2011.00059
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发表时间：
2012-01-01
影响因子：
4.8
通讯作者：
Di Giovanni, Simone
中科院分区：
文献类型：
--
作者：
Puttagunta, Radhika;Di Giovanni, Simone
急性中枢神经系统（CNS）损伤后，轴突再生和功能恢复极其有限。这是由于外在抑制生长环境和缺乏内在生长能力造成的。视黄酸 (RA) 信号对于脊髓运动神经元的背腹侧模式形成和规范至关重要，已被证明通过其受体（转录因子 RA 受体 β 2 (RAR β 2)）诱导脊髓损伤 (SCI) 后的轴突再生。最近，研究表明，在背根神经节神经元 (DRG) 中，慢病毒 RAR beta 2 表达大大增加了 cAMP 水平，并有助于神经突生长。此外，RAR β 激动剂在小脑颗粒神经元 (CGN) 和体内大脑中诱导 AKT 磷酸肌醇 3 激酶依赖性磷酸化，从而参与 RAR β 依赖性神经突生长。最近，研究表明，在体外轴突生长抑制环境下以及体内脊髓损伤后，RA-RAR β 途径可直接转录抑制抑制性 Nogo 受体 (NgR) 复合物的成员 Lingo-1。这一观点重点关注这些新发现的分子机制和该领域的未来方向。
Following an acute central nervous system (CNS) Injury, axonal regeneration and functional recovery are extremely limited. This is due to an extrinsic inhibitory growth environment and the lack of intrinsic growth competence. Retinoic acid (RA) signaling, essential in developmental dorsoventral patterning and specification of spinal motor neurons, has been shown through its receptor, the transcription factor RA receptor beta 2 (RAR beta 2), to induce axonal regeneration following spinal cord injury (SCI). Recently, it has been shown that in dorsal root ganglion neurons (DRGs), cAMP levels were greatly increased by lentiviral RAR beta 2 expression and contributed to neurite outgrowth. Moreover, RAR beta agonists, in cerebellar granule neurons (CGN) and in the brain in vivo, induced phosphoinositide 3-kinase dependent phosphorylation of AKT that was involved in RAR beta-dependent neurite outgrowth. More recently, RA-RAR beta pathways were shown to directly transcriptionally repress a member of the inhibitory Nogo receptor (NgR) complex, Lingo-1, under an axonal growth inhibitory environment in vitro as well as following spinal injury in vivo. This perspective focuses on these newly discovered molecular mechanisms and future directions in the field.