Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System

Abstract

Hyaluronic acid (HA) plays a vital role in the extracellular matrix of neural tissues. Originally thought to hydrate tissues and provide mechanical support, it is now clear that HA is also a complex signaling molecule that can regulate cell processes in the developing and adult nervous systems. Signaling properties are determined by molecular weight, bound proteins, and signal transduction through specific receptors. HA signaling regulates processes such as proliferation, differentiation, migration, and process extension in a variety of cell types including neural stem cells, neurons, astrocytes, microglia, and oligodendrocyte progenitors. The synthesis and catabolism of HA and the expression of HA receptors are altered in disease and influence neuroinflammation and disease pathogenesis. This review discusses the roles of HA, its synthesis and breakdown, as well as receptor expression in neurodevelopment, nervous system function and disease.

Multispectral LEDs Eliminate Lipofuscin-Associated Autofluorescence for Immunohistochemistry and CD44 Variant Detection by in Situ Hybridization in Aging Human, non-Human Primate, and Murine Brain

“…Fluorescence CD44 variant detection in aging human white matter. The CD44 transmembrane glycoprotein has been implicated in neuroinflammatory and neurodegenerative diseases and brain aging in humans ( Peters and Sherman, 2020 ). The human CD44 gene includes 9 variant exons (v2-v10) that generate alternative RNA splice variants encoding diverse CD44 proteins.…”

“…Our analysis of novel CD44 variant expression in aging-associated human cerebral white matter lesions demonstrates that LAF posed significant challenges to validate our results. Although CD44 contributes to inflammatory-mediated responses to cerebral injury ( Peters and Sherman, 2020 ) as well as CNS tumor progression ( Nagasaka et al, 1995 ; Jijiwa et al, 2011 ), the role of CD44 variants in the response to human white matter injury has not been defined. Alternative RNA splicing generates multiple CD44 variants, which involves nine exons in humans ( Chen et al, 2018 ).…”

A glial perspective on the extracellular matrix and perineuronal net remodeling in the central nervous system

“…Astrocytes are the predominant source of hyaluronan that constitutes the interstitial matrix and PNNs in the gray matter and surrounds the myelinated fibers in white matter ( Cargill et al, 2012 ; Peters and Sherman, 2020 ). Since hyaluronan chains of the PNN extend from the neuronal surface-bound HAS ( Fawcett et al, 2019 ), neurons appear to be a predominant source of PNN-forming hyaluronan.…”

Natural Biopolymers as Additional Tools for Cell Microencapsulation Applied to Cellular Therapy

“…It is a Glycosaminoglycan (GAG) family polymer found in all vertebrates, mainly in the extracellular matrix of connective tissues [65]. This compound exhibits high biocompatibility and biodegradability due to its ubiquitous distribution in the human body and plays an important role in cell division, differentiation and migration [66]. In addition, it is associated with angiogenesis [67], would healing [68], skin rejuvenation [69] and injury tissue regeneration [70,71], and it can be employed in drug delivery [72].…”