Abstract

The process of uncontrolled internal scarring, called fibrosis, is now emerging as a pathological feature shared by both peripheral and central nervous system diseases. In the CNS, damaged neurons are not replaced by tissue regeneration, and scar-forming cells such as endothelial cells, inflammatory immune cells, stromal fibroblasts, and astrocytes can persist chronically in brain and spinal cord lesions. Although this process was extensively described in acute CNS damages, novel evidence indicates the involvement of a fibrotic reaction in chronic CNS injuries as those occurring during neurodegenerative diseases, where inflammation and fibrosis fuel degeneration. In this mini review, we discuss recent advances around the role of fibrotic scar formation and function in different neurodegenerative conditions, particularly focusing on the rising role of scarring in the pathogenesis of amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's disease and highlighting the therapeutic relevance of targeting fibrotic scarring to slow and reverse neurodegeneration.

Highlights

  • Fibrosis identifies a condition marked by an increase of interstitial fibrous tissue in the parenchyma, induced by an uncontrolled inflammatory reaction derived by a wound healing response to tissue injury

  • Called mesenchymal scarring, represents the central core of the CNS acute lesions and it mainly consists of endothelial cells and inflammatory immune cells, including monocyte-derived macrophages, stromal fibroblasts, and extracellular matrix (ECM) deposits

  • Elevated levels of connective tissue growth factor (CTGF) a protein involved in different processes, among which adhesion, migration, and synthesis of ECM components is increased in the spinal cord of amyotrophic lateral sclerosis (ALS) patients [32]

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Summary

Introduction

Fibrosis identifies a condition marked by an increase of interstitial fibrous tissue in the parenchyma, induced by an uncontrolled inflammatory reaction derived by a wound healing response to tissue injury. Called mesenchymal scarring, represents the central core of the CNS acute lesions and it mainly consists of endothelial cells and inflammatory immune cells, including monocyte-derived macrophages, stromal fibroblasts, and ECM deposits.

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