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

• Published in: International journal of molecular sciences Vol. 22; no. 11; p. 5583
• Main Authors: Melrose, James, Hayes, Anthony J, Bix, Gregory
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 25.05.2021; MDPI AG
• Subjects: agrin; Animals; Central Nervous System - enzymology; Central Nervous System - metabolism; Central Nervous System - physiology; extracellular matrix; Extracellular Matrix - metabolism; Humans; Hyaluronic Acid - metabolism; Nerve Net - enzymology; Nerve Net - metabolism; Nerve Net - physiology; Neurogenesis - genetics; Neurogenesis - physiology; Neurons - metabolism; NG2 proteoglycan; Peripheral Nervous System - enzymology; Peripheral Nervous System - metabolism; Peripheral Nervous System - physiology; perlecan; phosphacan; proteoglycans; Proteoglycans - metabolism; Review; Signal Transduction - genetics; Signal Transduction - physiology; Neuroglycan-C; phosphacan; proteoglycans; neural repair and regeneration1; NG2 proteoglycan; lecticans; agrin; hyaluronan; perlecan; extracellular matrix
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22115583

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