Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a non-cell autonomous motor neuron loss. While it is generally believed that the disease onset takes place inside motor neurons, different cell types mediating neuroinflammatory processes are considered deeply involved in the progression of the disease. On these grounds, many treatments have been tested on ALS animals with the aim of inhibiting or reducing the pro-inflammatory action of microglia and astrocytes and counteract the progression of the disease. Unfortunately, these anti-inflammatory therapies have been only modestly successful. The non-univocal role played by microglia during stress and injuries might explain this failure. Indeed, it is now well recognized that, during ALS, microglia displays different phenotypes, from surveillant in early stages, to activated states, M1 and M2, characterized by the expression of respectively harmful and protective genes in later phases of the disease. Consistently, the inhibition of microglial function seems to be a valid strategy only if the different stages of microglia polarization are taken into account, interfering with the reactivity of microglia specifically targeting only the harmful pathways and/or potentiating the trophic ones. In this review article, we will analyze the features and timing of microglia activation in the light of M1/M2 phenotypes in the main mice models of ALS. Moreover, we will also revise the results obtained by different anti-inflammatory therapies aimed to unbalance the M1/M2 ratio, shifting it towards a protective outcome.

Geloso, M. C., Corvino, V., Marchese, E., Serrano, A., Michetti, F., D'Ambrosi, N., The Dual Role of Microglia in ALS: Mechanisms and Therapeutic Approaches., <<FRONTIERS IN AGING NEUROSCIENCE>>, 2017; (9:242): 1-10. [doi:10.3389/fnagi.2017.00242] [http://hdl.handle.net/10807/115006]

The Dual Role of Microglia in ALS: Mechanisms and Therapeutic Approaches.

Geloso, Maria Concetta
Primo
;
Corvino, Valentina
Secondo
;
Marchese, Elisa;Serrano, Alessia;Michetti, Fabrizio
Penultimo
;
2017

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a non-cell autonomous motor neuron loss. While it is generally believed that the disease onset takes place inside motor neurons, different cell types mediating neuroinflammatory processes are considered deeply involved in the progression of the disease. On these grounds, many treatments have been tested on ALS animals with the aim of inhibiting or reducing the pro-inflammatory action of microglia and astrocytes and counteract the progression of the disease. Unfortunately, these anti-inflammatory therapies have been only modestly successful. The non-univocal role played by microglia during stress and injuries might explain this failure. Indeed, it is now well recognized that, during ALS, microglia displays different phenotypes, from surveillant in early stages, to activated states, M1 and M2, characterized by the expression of respectively harmful and protective genes in later phases of the disease. Consistently, the inhibition of microglial function seems to be a valid strategy only if the different stages of microglia polarization are taken into account, interfering with the reactivity of microglia specifically targeting only the harmful pathways and/or potentiating the trophic ones. In this review article, we will analyze the features and timing of microglia activation in the light of M1/M2 phenotypes in the main mice models of ALS. Moreover, we will also revise the results obtained by different anti-inflammatory therapies aimed to unbalance the M1/M2 ratio, shifting it towards a protective outcome.
2017
Inglese
Geloso, M. C., Corvino, V., Marchese, E., Serrano, A., Michetti, F., D'Ambrosi, N., The Dual Role of Microglia in ALS: Mechanisms and Therapeutic Approaches., <<FRONTIERS IN AGING NEUROSCIENCE>>, 2017; (9:242): 1-10. [doi:10.3389/fnagi.2017.00242] [http://hdl.handle.net/10807/115006]
File in questo prodotto:
File Dimensione Formato  
fnagi-09-00242.pdf

accesso aperto

Tipologia file ?: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 1.33 MB
Formato Adobe PDF
1.33 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/115006
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 148
  • ???jsp.display-item.citation.isi??? 147
social impact