Collagen VI in healthy and diseased nervous system.

Ilaria Gregorio,Matilde Cescon,Paola Braghetta,Paolo Bonaldo

doi:10.1242/dmm.032946

Abstract

ABSTRACTCollagen VI is a major extracellular matrix protein exerting a number of functions in different tissues, spanning from biomechanical to regulatory signals in the cell survival processes, and playing key roles in maintaining the stemness or determining the differentiation of several types of cells. In the last couple of years, emerging findings on collagen VI have led to increased interest in its role in the nervous system. The role of this protein in the peripheral nervous system was intensely studied and characterized in detail. Collagen VI acts as a regulator of Schwann cell differentiation and is required for preserving peripheral nerve myelination, function and structure, as well as for orchestrating nerve regeneration after injury. Although the role and distribution of collagen VI in the peripheral nervous system is now well established, the role of this distinctive extracellular matrix component in the central nervous system, along with its links to human neurological and neurodegenerative disorders, remains an open field of investigation. In this Review, we summarize and discuss a number of recent findings related to collagen VI in the central and peripheral nervous systems. We further link these findings to different aspects of the protein that are relevant to human diseases in these compartments in order to provide a comprehensive overview of the roles of this key matrix component in the nervous system.

Highlights

Collagen VI (ColVI) is a broadly distributed extracellular matrix (ECM; see Glossary, Box 1) protein with a number of unique structural and functional features
Using wild-type and Col6a1−/− mice, we found that the COL6 genes were upregulated during aging and demonstrated that geriatric (23-month-old) ColVI-null mice displayed a higher incidence of apoptosis, higher oxidative damage and altered autophagic flux in neuronal cells compared with age-matched wild-type mice
Conclusions a growing number of studies are increasingly highlighting the distinct roles of ColVI in the nervous system, much work remains to be done to reach a more detailed understanding of the functions of this protein in the central nervous system (CNS) and peripheral nervous system (PNS)

Summary

Introduction

Collagen VI (ColVI) is a broadly distributed extracellular matrix (ECM; see Glossary, Box 1) protein with a number of unique structural and functional features. These recent findings were based on studies in animal models (Box 2) and genetic analyses in humans, linking ColVI gene variants to disorders of the nervous system In this Review, we first provide an overview of previous and new findings on ColVI in the central nervous system (CNS), as well as its roles and functions in the peripheral nervous system (PNS). Tissue, mainly consisting of the basal lamina associated with the meninges and the brain blood vessels, as well as in the nervous tissue itself, in the form of perineuronal nets and the neural interstitial matrix dispersed in the parenchyma (Box 1) (Lau et al, 2013).

C2 C3 C4

Conclusions