The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

Int J Mol Sci. 2021 May 25;22(11):5583. doi: 10.3390/ijms22115583.

Abstract

Background: The extracellular matrix of the PNS/CNS is unusual in that it is dominated by glycosaminoglycans, especially hyaluronan, whose space filling and hydrating properties make essential contributions to the functional properties of this tissue. Hyaluronan has a relatively simple structure but its space-filling properties ensure micro-compartments are maintained in the brain ultrastructure, ensuring ionic niches and gradients are maintained for optimal cellular function. Hyaluronan has cell-instructive, anti-inflammatory properties and forms macro-molecular aggregates with the lectican CS-proteoglycans, forming dense protective perineuronal net structures that provide neural and synaptic plasticity and support cognitive learning.

Aims: To highlight the central nervous system/peripheral nervous system (CNS/PNS) and its diverse extracellular and cell-associated proteoglycans that have cell-instructive properties regulating neural repair processes and functional recovery through interactions with cell adhesive molecules, receptors and neuroregulatory proteins. Despite a general lack of stabilising fibrillar collagenous and elastic structures in the CNS/PNS, a sophisticated dynamic extracellular matrix is nevertheless important in tissue form and function.

Conclusions: This review provides examples of the sophistication of the CNS/PNS extracellular matrix, showing how it maintains homeostasis and regulates neural repair and regeneration.

Keywords: NG2 proteoglycan; Neuroglycan-C; agrin; extracellular matrix; hyaluronan; lecticans; neural repair and regeneration1; perlecan; phosphacan; proteoglycans.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System / enzymology
  • Central Nervous System / metabolism*
  • Central Nervous System / physiology
  • Extracellular Matrix / metabolism*
  • Humans
  • Hyaluronic Acid / metabolism
  • Nerve Net / enzymology
  • Nerve Net / metabolism*
  • Nerve Net / physiology
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Neurons / metabolism*
  • Peripheral Nervous System / enzymology
  • Peripheral Nervous System / metabolism*
  • Peripheral Nervous System / physiology
  • Proteoglycans / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Proteoglycans
  • Hyaluronic Acid