College of Life Science, China West Normal University , Nanchong , China and.
J Drug Target. 2014 Jun;22(5):365-71. doi: 10.3109/1061186X.2013.878939. Epub 2014 Jan 9.
A major barrier to axonal regeneration in mammals is the unfavorable extracellular environment that develops following injury to the central nervous system (CNS). In particular, three myelin-associated inhibitory proteins (MAIs) - Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp) - are known to inhibit axonal regeneration and functional recovery. These MAIs share a common receptor, glycosylphosphatidylinositol-anchored Nogo receptor (NgR). However, paired immunoglobulin-like receptor B (PirB) - which was originally identified as a receptor for class I major histocompatibility complex (MHCI) in the immune system - is also expressed in neurones and plays a similarly inhibitory role in axonal regeneration and synaptic plasticity following CNS injury through its association with MAIs. Importantly, suppression of PirB activity through antibody antagonism or genetic means can partially relieve the inhibition of neurite outgrowth in vitro and in vivo. In this review, we present the molecular features, expression patterns and known signaling pathways of PirB, and we specifically focus on putative roles for PirB in the CNS and its potential as a target of molecular therapies for enhancing axonal regeneration and synaptic plasticity following CNS injury.
哺乳动物轴突再生的主要障碍是中枢神经系统（CNS）损伤后形成的不利细胞外环境。特别是三种髓鞘相关抑制蛋白（MAIs）-Nogo、髓鞘相关糖蛋白（MAG）和少突胶质细胞髓鞘糖蛋白（OMgp）-已知会抑制轴突再生和功能恢复。这些 MAIs 具有共同的受体，糖基磷脂酰肌醇锚定的 Nogo 受体（NgR）。然而，配对免疫球蛋白样受体 B（PirB）-最初在免疫系统中被鉴定为 I 类主要组织相容性复合体（MHCI）的受体-也在神经元中表达，并通过与 MAIs 结合在 CNS 损伤后轴突再生和突触可塑性中发挥类似的抑制作用。重要的是，通过抗体拮抗或遗传手段抑制 PirB 活性可以部分缓解体外和体内神经突生长的抑制。在这篇综述中，我们介绍了 PirB 的分子特征、表达模式和已知的信号通路，并且特别关注了 PirB 在中枢神经系统中的潜在作用及其作为增强 CNS 损伤后轴突再生和突触可塑性的分子治疗靶点的潜力。
