Are Circulating Cytokines Reliable Biomarkers for Amyotrophic Lateral Sclerosis?

Moreno-Martínez, Laura; Calvo, Ana C.; Muñoz, Marı́a Jesús; Osta, Rosario

doi:10.3390/ijms20112759

Cited by 36 publications

(36 citation statements)

References 112 publications

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“…24 While plasma MCP-1, IL-18, and sTREM2 are higher in the fast-progression groups, IL-15 in plasma shows the opposite trend, likely reflecting the complexity of adaptive immune system regulation depending on disease stage. 6,32,36 This report is the first to analyze a comprehensive panel of cytokines in longitudinal PALS CSF samples. We demonstrate the general stability of MCP-1 and IL-18 levels in both CSF and plasma over the course of disease.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal biomarkers in amyotrophic lateral sclerosis

Huang

Zhu

Hsiao‐Nakamoto

et al. 2020

Ann Clin Transl Neurol

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Section: Discussionmentioning

confidence: 99%

Longitudinal biomarkers in amyotrophic lateral sclerosis

Huang

Zhu

Hsiao‐Nakamoto

et al. 2020

Ann Clin Transl Neurol

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“…Among the mechanisms involved in neuronal death, neuroinflammation is one of the most established factors. ALS patients present alterations in levels of a range of pro-inflammatory cytokines in the cerebrospinal fluid (Mitchell et al, 2009;Moreno-Martinez et al, 2019), as well as increased rates of reactive cerebral microglial cells (Turner et al, 2004). Depending on the stage of the disease, reactive microglia with protective or cytotoxic properties is found, demonstrating the complexity of neuroinflammation in this disorder (Evans et al, 2013).…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

The P2X7 Receptor: Central Hub of Brain Diseases

Andrejew

Oliveira-Giacomelli

Ribeiro

et al. 2020

Front. Mol. Neurosci.

112

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The P2X7 receptor is a cation channel activated by high concentrations of adenosine triphosphate (ATP). Upon long-term activation, it complexes with membrane proteins forming a wide pore that leads to cell death and increased release of ATP into the extracellular milieu. The P2X7 receptor is widely expressed in the CNS, such as frontal cortex, hippocampus, amygdala and striatum, regions involved in neurodegenerative diseases and psychiatric disorders. Despite P2X7 receptor functions in glial cells have been extensively studied, the existence and roles of this receptor in neurons are still controversially discussed. Regardless, P2X7 receptors mediate several processes observed in neuropsychiatric disorders and brain tumors, such as activation of neuroinflammatory response, stimulation of glutamate release and neuroplasticity impairment. Moreover, P2X7 receptor gene polymorphisms have been associated to depression, and isoforms of P2X7 receptors are implicated in neuropsychiatric diseases. In view of that, the P2X7 receptor has been proposed to be a potential target for therapeutic intervention in brain diseases. This review discusses the molecular mechanisms underlying P2X7 receptor-mediated signaling in neurodegenerative diseases, psychiatric disorders, and brain tumors. In addition, it highlights the recent advances in the development of P2X7 receptor antagonists that are able of penetrating the central nervous system.

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“…However, only a small number of microglial factors have been directly shown to confer neuroprotection in models of ALS. Several microglia-related cytokines associated with neuroprotection including IL-4, IL-10 and G-CSF have been reported to be altered in ALS patients and models ( Jeyachandran et al , 2015 ; Lu et al , 2016 ; Moreno-Martinez et al , 2019 a , b ). Lentiviral delivery of IL-4 before the onset of disease in mSOD1 mice increased expression of other reportedly neuroprotective genes including Arg1 , Retnla (Fizz1) and Chil3 (Ym1) and decreased genes associated with neurotoxicity including Tnfa , Ifng and Il1b ( Rossi et al , 2018 ).…”

Section: Microglial Molecular Changes In Alsmentioning

confidence: 99%

The microglial component of amyotrophic lateral sclerosis

Clarke

Patani

2020

Brain

102

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Microglia are the primary immune cells of the CNS, carrying out key homeostatic roles and undergoing context-dependent and temporally regulated changes in response to injury and neurodegenerative diseases. Microglia have been implicated in playing a role in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by extensive motor neuron loss leading to paralysis and premature death. However, as the pathomechansims of ALS are increasingly recognized to involve a multitude of different cell types, it has been difficult to delineate the specific contribution of microglia to disease. Here, we review the literature of microglial involvement in ALS and discuss the evidence for the neurotoxic and neuroprotective pathways that have been attributed to microglia in this disease. We also discuss accumulating evidence for spatiotemporal regulation of microglial activation in this context. A deeper understanding of the role of microglia in the ‘cellular phase’ of ALS is crucial in the development of mechanistically rationalized therapies.

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Are Circulating Cytokines Reliable Biomarkers for Amyotrophic Lateral Sclerosis?

Cited by 36 publications

References 112 publications

Longitudinal biomarkers in amyotrophic lateral sclerosis

Longitudinal biomarkers in amyotrophic lateral sclerosis

The P2X7 Receptor: Central Hub of Brain Diseases

The microglial component of amyotrophic lateral sclerosis

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