Fibrotic Scar in Neurodegenerative Diseases

Frontiers in Immunology, 2020 · DOI: 10.3389/ﬁmmu.2020.01394 · Published: August 14, 2020

Simple Explanation

Fibrosis, or uncontrolled internal scarring, is increasingly recognized as a pathological feature in both the peripheral and central nervous systems. In the CNS, unlike other tissues, damaged neurons are not replaced, leading to persistent scar formation by cells like endothelial cells, immune cells, fibroblasts, and astrocytes. In chronic CNS injuries, such as those in neurodegenerative diseases, inflammation and fibrosis exacerbate degeneration. This review focuses on the role of fibrotic scar formation in diseases like amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease. The review explores the therapeutic potential of targeting fibrotic scarring to slow or reverse neurodegeneration, highlighting recent advances in understanding the function of fibrotic scars in various neurodegenerative conditions.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Fibrotic scarring in neurodegenerative diseases like ALS, MS, and AD involves complex interactions between various cell types, including astrocytes, microglia, fibroblasts, and immune cells.
2
The extracellular matrix (ECM) plays a crucial role in fibrotic scar formation, with components like fibronectin, collagen, and proteoglycans contributing to the scar's structure and function.
3
Targeting fibrotic scarring mechanisms, such as inflammation, autophagy, and mesenchymal reactivity, may offer potential therapeutic strategies for neurodegenerative diseases.

Research Summary

This mini-review discusses the role of fibrotic scar formation in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer’s disease (AD). The review highlights that in chronic neurodegenerative diseases, there is a progressive replacement of damaged tissue with ECM components, produced by activated fibroblasts and astrocytes, leading to a secondary response involving microglia and peripheral immune cells. The authors suggest that therapeutic strategies aimed at removing excessive fibrotic matrix and slowing down ECM deposition could be promising in limiting chronic inflammation associated with fibrosis, potentially improving the outcome of neurodegenerative diseases.

Practical Implications

Therapeutic Targeting

Targeting fibrotic scar formation could be a novel therapeutic avenue for neurodegenerative diseases.

Multifactorial Treatment

Successful treatment of neurodegenerative diseases requires multi-targeted approaches.

Regeneration Improvement

Modifying scarring to promote axon regeneration may improve disease outcomes.

Study Limitations

1
The review acknowledges that glial functions are complex and not easily categorized, with responses being simultaneously detrimental and protective.
2
The exact mechanisms by which ECM remodeling contributes to disease progression in ALS, MS and AD are not fully understood.
3
The review relies on existing literature and may be limited by the scope and availability of published studies.

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