TY - JOUR
T1 - The Dual Role of Microglia in ALS: Mechanisms and Therapeutic Approaches.
AU - Geloso, Maria Concetta
AU - Corvino, Valentina
AU - Marchese, Elisa
AU - Serrano, Alessia
AU - Michetti, Fabrizio
AU - D'Ambrosi, Nadia
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - M1/M2 microglia
KW - amyotrophic lateral sclerosis
KW - anti-inflammatory drugs
KW - genetic modifiers
KW - mutant SOD1 mice
KW - neuroinflammation
KW - M1/M2 microglia
KW - amyotrophic lateral sclerosis
KW - anti-inflammatory drugs
KW - genetic modifiers
KW - mutant SOD1 mice
KW - neuroinflammation
UR - http://hdl.handle.net/10807/115006
U2 - 10.3389/fnagi.2017.00242
DO - 10.3389/fnagi.2017.00242
M3 - Article
SN - 1663-4365
SP - 1
EP - 10
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
ER -