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.
Chemotherapy‐induced peripheral neuropathy (CIPN) is a common side effect during the course of cancer treatment, which is mainly manifested as a series of sensory abnormalities. At present, there are no recommended prevention or treatment strategies, and the underlying mechanisms are unclear. The ketogenic diet (KD), a special diet that is high in fat and low in carbohydrate intake, shows good therapeutic potential in children with epilepsy. In this study, it was found that KD significantly prevented paclitaxel‐induced neuropathic nociception. Using the GSE113941 database, 281 differentially expressed genes (DEGs) were found in an animal model of CIPN and controls. The DEGs were mainly enriched in peroxisome proliferator activated receptor (PPAR) and oxidative phosphorylation signalling pathways. As a main regulatory pathway of lipid metabolism, the PPARγ signalling pathway was significantly upregulated in the KD model. In addition, KD also inhibited the expression of pro‐inflammatory cytokines and the TLR4/NF‐κB signalling pathway in the dorsal root ganglion (DRG) in paclitaxel‐treated rats. In vitro, rat primary DRG neurons were used to investigate the role of PPARγ in paclitaxel‐induced neurotoxicity. It was found that PPARγ agonist rosiglitazone significantly protected DRG neurons against cell apoptosis and reactive oxygen species generation induced by paclitaxel administration. Therefore, KD is a prospective treatment option when applied as a dietary intervention in the prevention and treatment of paclitaxel‐induced neuropathic nociception, possibly through the activation of PPARγ and its neuroprotective functions.
Cerebral ischemia may cause irreversible neural network damage and result in functional deficits. Targeting neuronal repair after stroke potentiates the formation of new connections, which can be translated into a better functional outcome. Innate and adaptive immune responses in the brain and the periphery triggered by ischemic damage participate in regulating neural repair after a stroke. Immune cells in the blood circulation and gut lymphatic tissues that have been shaped by immune components including gut microbiota and metabolites can infiltrate the ischemic brain and, once there, influence neuronal regeneration either directly or by modulating the properties of brain-resident immune cells. Immune-related signalings and metabolites from the gut microbiota can also directly alter the phenotypes of resident immune cells to promote neuronal regeneration. In this review, we discuss several potential mechanisms through which peripheral and brain-resident immune components can cooperate to promote first the resolution of neuroinflammation and subsequently to improved neural regeneration and a better functional recovery. We propose that new insights into discovery of regulators targeting pro-regenerative process in this complex neuro-immune network may lead to novel strategies for neuronal regeneration.
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