Chondroitin sulfate proteoglycans (CSPGs), extracellular matrix molecules that increase dramatically following a variety of CNS injuries or diseases, have long been known for their potent capacity to curtail cell migrations as well as axon regeneration and sprouting. The inhibition can be conferred through binding to their major cognate receptor, Protein Tyrosine Phosphatase Sigma (PTPσ). However, the precise mechanisms downstream of receptor binding that mediate growth inhibition have remained elusive. Recently, CSPGs/PTPσ interactions were found to regulate autophagic flux at the axon growth cone by dampening the autophagosome-lysosomal fusion step. Because of the intense interest in autophagic phenomena in the regulation of a wide variety of critical cellular functions, we summarize here what is currently known about dysregulation of autophagy following spinal cord injury, and highlight this critical new mechanism underlying axon regeneration failure. Furthermore, we review how CSPGs/PTPσ interactions influence plasticity through autophagic regulation and how PTPσ serves as a switch to execute either axon outgrowth or synaptogenesis. This has exciting implications for the role CSPGs play not only in axon regeneration failure after spinal cord injury, but also in neurodegenerative diseases where, again, inhibitory CSPGs are upregulated.

中文翻译：

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抑制CSPG与受体PTPσ相互作用对自噬的调节及其对脊髓损伤后可塑性和再生的影响。

硫酸软骨素蛋白聚糖（CSPG）是在各种CNS损伤或疾病后急剧增加的细胞外基质分子，长期以来因其有效的抑制细胞迁移以及轴突再生和发芽的能力而闻名。可以通过与它们的主要同源受体蛋白酪氨酸磷酸酶Sigma（PTPσ）结合来实现抑制作用。但是，受体结合下游介导生长抑制的确切机制仍然难以捉摸。最近，发现CSPGs /PTPσ相互作用通过抑制自噬体-溶酶体融合步骤来调节轴突生长锥处的自噬通量。由于自噬现象对调节多种关键细胞功能的浓厚兴趣，我们在这里总结了目前关于脊髓损伤后自噬失调的已知信息，并着重介绍了轴突再生失败背后的这一关键新机制。此外，我们审查了CSPGs /PTPσ相互作用如何通过自噬调节作用影响可塑性，以及PTPσ如何充当执行轴突生长或突触形成的开关。这对于CSPG不仅在脊髓损伤后轴突再生失败中起着作用，而且在神经退行性疾病中也起抑制作用CSPG上调的作用具有令人兴奋的意义。我们回顾了CSPGs /PTPσ相互作用如何通过自噬调节影响可塑性，以及PTPσ如何充当执行轴突生长或突触形成的开关。这对于CSPG不仅在脊髓损伤后轴突再生失败中起着作用，而且在神经退行性疾病中也起抑制作用CSPG上调的作用具有令人兴奋的意义。我们回顾了CSPGs /PTPσ相互作用如何通过自噬调节影响可塑性，以及PTPσ如何充当执行轴突生长或突触形成的开关。这对于CSPG不仅在脊髓损伤后轴突再生失败中起着作用，而且在神经退行性疾病中也起抑制作用CSPG上调的作用具有令人兴奋的意义。