The role of inflammation in neurodegeneration: novel insights into the role of the immune system in C9orf72 HRE-mediated ALS/FTD

Pegah Masrori; Jimmy Beckers; Helena Gossye; Philip Van Damme

doi:10.1186/s13024-022-00525-z

The role of inflammation in neurodegeneration: novel insights into the role of the immune system in C9orf72 HRE-mediated ALS/FTD

Mol Neurodegener. 2022 Mar 18;17(1):22. doi: 10.1186/s13024-022-00525-z.

Authors

Pegah Masrori^#^{1

2

3

4}, Jimmy Beckers^#^{1

2}, Helena Gossye^{4

5

6}, Philip Van Damme^{7

8

9}

Affiliations

¹ Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, 3000, Leuven, Belgium.
² Laboratory of Neurobiology, Experimental Neurology, Center for Brain and Disease Research, VIB, Campus Gasthuisberg, O&N5, Herestraat 49, 602, 3000, Leuven, PB, Belgium.
³ Neurology Department, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium.
⁴ Department of Neurology, University Hospital Antwerp, 2650, Edegem, Belgium.
⁵ VIB Center for Molecular Neurology, Neurodegenerative Brain Diseases, University of Antwerp, 2000, Antwerp, Belgium.
⁶ Department of Biomedical Sciences, University of Antwerp, 2000, Antwerp, Belgium.
⁷ Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, 3000, Leuven, Belgium. philip.vandamme@kuleuven.be.
⁸ Laboratory of Neurobiology, Experimental Neurology, Center for Brain and Disease Research, VIB, Campus Gasthuisberg, O&N5, Herestraat 49, 602, 3000, Leuven, PB, Belgium. philip.vandamme@kuleuven.be.
⁹ Neurology Department, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. philip.vandamme@kuleuven.be.

^# Contributed equally.

Abstract

Neuroinflammation is an important hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). An inflammatory reaction to neuronal injury is deemed vital for neuronal health and homeostasis. However, a continued activation of the inflammatory response can be detrimental to remaining neurons and aggravate the disease process. Apart from a disease modifying role, some evidence suggests that neuroinflammation may also contribute to the upstream cause of the disease. In this review, we will first focus on the role of neuroinflammation in the pathogenesis of chromosome 9 open reading frame 72 gene (C9orf72) hexanucleotide repeat expansions (HRE)-mediated ALS/FTD (C9-ALS/FTD). Additionally, we will discuss evidence from ex vivo and in vivo studies and finally, we briefly summarize the trials and progress of anti-inflammatory therapies.

Keywords: Anti-inflammatory therapies; Astrocytes; C9orf72 HRE-mediated ALS/FTD; In-vivo and ex-vivo models; Microglia; Neuroinflammation; Peripheral immune cells.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Amyotrophic Lateral Sclerosis* / pathology
C9orf72 Protein / genetics
DNA Repeat Expansion / genetics
Frontotemporal Dementia* / pathology
Humans
Immune System
Inflammation / genetics

Substances

C9orf72 Protein
C9orf72 protein, human