中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (1): 26-35.doi: 10.4103/1673-5374.286948

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

组织蛋白酶在神经可塑性中的作用

  

  • 出版日期:2021-01-15 发布日期:2020-11-23

Cathepsins in neuronal plasticity

Amanda Phuong Tran1, Jerry Silver2, *   

  1. 1 Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, USA;  2 Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA
  • Online:2021-01-15 Published:2020-11-23
  • Contact: Jerry Silver, PhD, jxs10@case.edu.
  • Supported by:
    JS was funded by NINDS (NS25713), Brumagin-Nelson Fund, Kaneko Family Fund, and the Hong Kong Spinal Cord Injury Fund.

摘要: https://orcid.org/0000-0001-5002-2599 (Jerry Silver) 

Abstract: Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins, resulting in protein lysis. Cathepsins, specifically, encompass a class of at least twenty proteases with potent endopeptidase activity. They are located subcellularly in lysosomes, organelles responsible for the cell’s degradative and autophagic processes, and are vital for normal lysosomal function. Although cathepsins are involved in a multitude of cell signaling activities, this chapter will focus on the role of cathepsins (with a special emphasis on Cathepsin B) in neuronal plasticity. We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease. Importantly, we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury. It is well established that normal cathepsin activity is integral to the function of lysosomes. Without normal lysosomal function, autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy. Furthermore, controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity. This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled, localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.

Key words: axon regeneration, cathepsin, CSPGs, extracellular matrix, growth cone, lysosomes, neuronal plasticity, protease, remodeling, spinal cord injury, synaptogenesis