期刊
EXPERIMENTAL NEUROLOGY
卷 328, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2020.113276
关键词
PTP sigma; Autophagy; Autophagic flux; Axon regeneration; Lysosome; CSPGs; Spinal cord injury; Growth cone; Axonal dystrophy; Neural plasticity; Synaptogenesis; Neurodegeneration
资金
- NINDS [NS25713]
- Brumagin-Nelson Fund
- Kaneko Family Fund
- Hong Kong Spinal Cord Injury Fund
- King's Prize University Fellowship
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 (PTP sigma). However, the precise mechanisms downstream of receptor binding that mediate growth inhibition have remained elusive. Recently, CSPGs/PTP sigma 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/PTP sigma interactions influence plasticity through autophagic regulation and how PTP sigma 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.
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