Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by muscle weakness due to the degeneration of the upper and lower motor neurons. Neuroinflammation is known as a prominent pathological feature of ALS. Although neuroinflammation cannot trigger ALS, activated central nervous system (CNS) microglia and astrocytes, proinflammatory periphery monocytes/macrophages and T lymphocytes, and infiltrated monocytes/macrophages and T lymphocytes, as well as the immunoreactive molecules they release, are closely related to disease progression. The crosstalk between the peripheral and CNS immune components mentioned above significantly correlates with survival in patients with ALS. This review provides an update on the role of this crosstalk between the CNS and peripheral immune responses in ALS. Additionally, we discuss changes in the composition of gut microbiota because these can directly or indirectly influence this crosstalk. These recent advances may well provide innovative ways for targeting the molecules associated with this crosstalk and breaking the current treatment impasse in ALS.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease featuring the progressive degeneration of upper motor neurons (MNs) in the motor cortex and lower MNs in the brainstem and spinal cord, which leads to muscle weakness in the earliest stage of the disease, followed by a gradual loss of all muscle control and, eventually, death (Brown and Al-Chalabi, 2017)
When mSOD1 mice were bred with T-cell–deficient mice, the levels of neurotrophic factor, glial glutamate transporter, and insulinlike growth factor 1 (IGF-1) in the spinal cord were decreased, but at the same time, the levels of proinflammatory cytokines and NOX2 were increased (Beers et al, 2008; Chiu et al, 2008). These findings show that reconstruction of CD4+ T-cell populations in animals can confer a degree of neuroprotection by regulating the glial balance between neurotrophic effect and cytotoxicity and that the immune response mediated by CD4+ T cells/microglia interactions plays a vital neuroprotective role in ALS mice (Beers et al, 2008; Chiu et al, 2008)
This review summarizes our current knowledge of the mechanisms that contribute to neuroinflammation in ALS
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease featuring the progressive degeneration of upper motor neurons (MNs) in the motor cortex and lower MNs in the brainstem and spinal cord, which leads to muscle weakness in the earliest stage of the disease, followed by a gradual loss of all muscle control and, eventually, death (Brown and Al-Chalabi, 2017).
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