Ablation of Proliferating Microglia Does Not Affect Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase

Gowing, Genevíève; Philips, Thomas; Wijmeersch, Bart Van; Audet, Josée; Dewil, Maarten; Bosch, Ludo Van Den; Billiau, An; Robberecht, Wim; Julien, J.P.

doi:10.1523/jneurosci.3494-08.2008

Cited by 129 publications

(116 citation statements)

References 63 publications

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“…A similar beneficial effect of microglia in stroke was reported in a study where there was a 60 % increase in infarct size by selective elimination of microglia, which the effect was reversed by repopulating the cells [65]. In contrast, microglia ablation was either protective or had no effect in models of other neurodegenerative diseases, including Alzheimer's disease [66], amyotrophic lateral sclerosis [67], and experimental autoimmune encephalomyelitis [68].…”

Section: Microgliasupporting

confidence: 65%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Section: Microgliasupporting

confidence: 65%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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“…Several authors suggest that peripheral monocytes infiltrate the ALS spinal cord contributing to motor neuron loss [107,108]. These results are inconsistent with previous parabiosis experiments that demonstrated no infiltration into the CNS from the periphery unless the blood-brain barrier was disrupted [84,[109][110][111][112]. However, monoctyes/macrophages have been demonstrated to aid in the inflammatory response of peripheral axons [113].…”

Section: Additional Peripheral Immune Contributionsmentioning

confidence: 85%

“…In the G93A mSOD1 transgenic mouse, activation of astrocytes occurs concomitantly with a decrease in motor neurons [75,82,83]. Although astrocyte numbers increase with disease progression, astrocytes do not proliferate like microglia, but may be derived from ependymal cells lining the central canal of the spinal cord or oligodendrocyte precursor cells [24,[84][85][86][87][88].…”

Section: Astrogliamentioning

confidence: 99%

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

et al. 2015

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Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disorder characterized by loss of motor neurons, resulting in paralysis and death. Multiple mechanisms of motor neuron injury have been implicated based upon the more than 20 different genetic causes of familial ALS. These inherited mutations compromise diverse motor neuron pathways leading to cell-autonomous injury. In the ALS transgenic mouse models, however, motor neurons do not die alone. Cell death is noncell-autonomous dependent upon a well orchestrated dialogue between motor neurons and surrounding glia and adaptive immune cells. The pathogenesis of ALS consists of 2 stages: an early neuroprotective stage and a later neurotoxic stage. During early phases of disease progression, the immune system is protective with glia and T cells, especially M2 macrophages/microglia, and T helper 2 cells and regulatory T cells, providing anti-inflammatory factors that sustain motor neuron viability. As the disease progresses and motor neuron injury accelerates, a second rapidly progressing phase develops, characterized by M1 macrophages/microglia, and proinflammatory T cells. In rapidly progressing ALS patients, as in transgenic mice, neuroprotective regulatory T cells are significantly decreased and neurotoxicity predominates. Our own therapeutic efforts are focused on modulating these neuroinflammatory pathways. This review will focus on the cellular players involved in neuroinflammation in ALS and current therapeutic strategies to enhance neuroprotection and suppress neurotoxicity with the goal of arresting the progressive and devastating nature of ALS.

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“…Moreover, when cocultured with motor neurons, microglia could cause cell death 49, 51. While much of the information points toward significant microglial contribution to disease, other reports have argued otherwise 52. Similarly, minocycline, a tetracycline derivative that has anti‐inflammatory properties in addition to off‐target inhibition of microglial activation, showed promise in preclinical models of ALS but failed in clinical trial 53, 54…”

Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 99%

New insights into SMA pathogenesis: immune dysfunction and neuroinflammation

Deguise

Kothary

2017

Ann Clin Transl Neurol

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Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by motor neuron degeneration, although defects in multiple cell types and tissues have also been implicated. Three independent laboratories recently identified immune organ defects in SMA. We therefore propose a novel pathogenic mechanism contributory to SMA, resulting in higher susceptibility to infection and exacerbated disease progression caused by neuroinflammation. Overall, compromised immune function could significantly affect survival and quality of life of SMA patients. We highlight the recent findings in immune organ defects, their potential consequences on patients, our understanding of neuroinflammation in SMA, and new research hypotheses in SMA pathogenesis.

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Ablation of Proliferating Microglia Does Not Affect Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase

Cited by 129 publications

References 63 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

New insights into SMA pathogenesis: immune dysfunction and neuroinflammation

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