LINGO-1 and AMIGO3, potential therapeutic targets for neurological and dysmyelinating disorders?
LINGO-1 and AMIGO3, potential therapeutic targets for neurological and dysmyelinating disorders?
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DOI：
10.4103/1673-5374.213538
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发表时间：
2017-08
影响因子：
6.1
通讯作者：
Ahmed Z
中科院分区：
文献类型：
--
作者：
Foale S;Berry M;Logan A;Fulton D;Ahmed Z
富含亮氨酸的重复序列蛋白由于其在中枢神经系统内的表达和生物活性而作为治疗靶点获得了相当大的兴趣。LINGO-1受到了特别的关注，因为它以RhoA依赖性方式抑制脊髓损伤后的轴突再生，同时抑制富含亮氨酸的重复序列和含有免疫球蛋白样结构域的蛋白1（LINGO-1）抑制神经元生长。此外，LINGO-1抑制少突胶质细胞前体细胞成熟和髓鞘产生。抑制LINGO-1的作用在体外和体内均促进髓鞘再生。因此，LINGO-1拮抗剂显示出作为脱髓鞘疾病的治疗的前景。LINGO-1的一种类似蛋白质，异丙肾上腺素诱导的基因和开放阅读框架3（AMIGO 3），对中枢神经系统神经元的轴突生长发挥相同的抑制作用，以及与LINGO-1相同的受体相互作用。然而，AMIGO 3在脊髓损伤后比LINGO-1更快地上调。我们推测AMIGO 3对少突胶质细胞前体细胞成熟和髓鞘生成具有与轴突生成相似的抑制作用。因此，抑制AMIGO 3将可能促进中枢神经系统轴突再生以及从局部少突胶质细胞前体细胞产生髓鞘，从而提供有希望的治疗靶点和未来研究的领域。
Leucine rich repeat proteins have gained considerable interest as therapeutic targets due to their expression and biological activity within the central nervous system. LINGO-1 has received particular attention since it inhibits axonal regeneration after spinal cord injury in a RhoA dependent manner while inhibiting leucine rich repeat and immunoglobulin-like domain-containing protein 1 (LINGO-1) disinhibits neuron outgrowth. Furthermore, LINGO-1 suppresses oligodendrocyte precursor cell maturation and myelin production. Inhibiting the action of LINGO-1 encourages remyelination both in vitro and in vivo. Accordingly, LINGO-1 antagonists show promise as therapies for demyelinating diseases. An analogous protein to LINGO-1, amphoterin-induced gene and open reading frame-3 (AMIGO3), exerts the same inhibitory effect on the axonal outgrowth of central nervous system neurons, as well as interacting with the same receptors as LINGO-1. However, AMIGO3 is upregulated more rapidly after spinal cord injury than LINGO-1. We speculate that AMIGO3 has a similar inhibitory effect on oligodendrocyte precursor cell maturation and myelin production as with axogenesis. Therefore, inhibiting AMIGO3 will likely encourage central nervous system axonal regeneration as well as the production of myelin from local oligodendrocyte precursor cell, thus providing a promising therapeutic target and an area for future investigation.
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影响因子：
4.3
作者：
Fujita Y;Yamashita T
通讯作者：
Yamashita T
DOI：
10.1073/pnas.0700901104
发表时间：
2007-09-04
影响因子：
11.1
作者：
Inoue, Haruhisa;Lin, Ling;Isacson, Ole
通讯作者：
Isacson, Ole
影响因子：
25
作者：
Mi, S;Lee, X;Pepinsky, RB
通讯作者：
Pepinsky, RB
DOI：
10.1016/j.mcn.2015.11.002
发表时间：
2016-01
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Meabon JS;de Laat R;Ieguchi K;Serbzhinsky D;Hudson MP;Huber BR;Wiley JC;Bothwell M
通讯作者：
Bothwell M
影响因子：
3.5
作者：
Bourikas, Dimitris;Mir, Anis;Walmsley, Adrian Robert
通讯作者：
Walmsley, Adrian Robert