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Review

Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity?

Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, via Ferrata 9, 27100 Pavia, Italy
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(21), 7923; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217923
Received: 30 September 2020 / Revised: 21 October 2020 / Accepted: 22 October 2020 / Published: 25 October 2020
(This article belongs to the Special Issue Proteotoxicity and Neurodegenerative Diseases)
Amyotrophic Lateral Sclerosis (ALS) is a complex pathology: (i) the neurodegeneration is chronic and progressive; it starts focally in specific central nervous system (CNS) areas and spreads to different districts; (ii) multiple cell types further than motor neurons (i.e., glial/immune system cells) are actively involved in the disease; (iii) both neurosupportive and neurotoxic neuroinflammatory responses were identified. Microglia cells (a key player of neuroinflammation in the CNS) attracted great interest as potential target cell population that could be modulated to counteract disease progression, at least in preclinical ALS models. However, the heterogeneous/multifaceted microglia cell responses occurring in different CNS districts during the disease represent a hurdle for clinical translation of single-drug therapies. To address this issue, over the past ten years, several studies attempted to dissect the complexity of microglia responses in ALS. In this review, we shall summarize these results highlighting how the heterogeneous signature displayed by ALS microglia reflects not only the extent of neuronal demise in different regions of the CNS, but also variable engagement in the attempts to cope with the neuronal damage. We shall discuss novel avenues opened by the advent of single-cell and spatial transcriptomics technologies, underlining the potential for discovery of novel therapeutic targets, as well as more specific diagnostic/prognostic not-invasive markers of neuroinflammation. View Full-Text
Keywords: neuroinflammation; microglia; single-cell RNAseq; spatial transcriptomics; PET neuroinflammation; microglia; single-cell RNAseq; spatial transcriptomics; PET
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MDPI and ACS Style

Cipollina, G.; Davari Serej, A.; Di Nolfi, G.; Gazzano, A.; Marsala, A.; Spatafora, M.G.; Peviani, M. Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity? Int. J. Mol. Sci. 2020, 21, 7923. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217923

AMA Style

Cipollina G, Davari Serej A, Di Nolfi G, Gazzano A, Marsala A, Spatafora MG, Peviani M. Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity? International Journal of Molecular Sciences. 2020; 21(21):7923. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217923

Chicago/Turabian Style

Cipollina, Giada, Arash Davari Serej, Gianluca Di Nolfi, Andrea Gazzano, Andrea Marsala, Mauro G. Spatafora, and Marco Peviani. 2020. "Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity?" International Journal of Molecular Sciences 21, no. 21: 7923. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217923

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