Circulating levels of tumour necrosis factor-α and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis

Poloni, M.; Facchetti, D.; Mai, Roberto; Micheli, A; Agnoletti, Laura; Francolini, Gloria; Mora, Gabriele; Camana, C.; Mazzini, Letizia; Bachetti, Tiziana

doi:10.1016/s0304-3940(00)01177-0

Cited by 184 publications

(129 citation statements)

References 14 publications

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“…In fact, expression of TNF-␣ correlates with the onset and progression of paralysis in mutant SOD1 mice (Elliott, 2001;Nguyen et al, 2001;Hensley et al, 2003). However, neither the presence of antigenic nor bioactive TNF-␣ correlated with disease severity, duration, or weight loss in ALS patients (Poloni et al, 2000). There is conflicting literature on the neuroprotective versus neurotoxic effect of TNF-␣ both in vivo and in vitro (Ghezzi and Mennini, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, gliosis is associated with an increase in the production of various potentially cytotoxic molecules, including reactive oxygen species, nitric oxide, proteases, and cytokines (Nguyen et al, 2002). Interestingly, an increased level of proinflammatory cytokines interleukin-1␤ (IL-1␤), IL-6, and tumor necrosis factor-␣ (TNF-␣) have been reported in SOD1 mice models and in ALS patients (Sekizawa et al, 1998;Poloni et al, 2000;Elliott, 2001;Nguyen et al, 2001;Hensley et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Absence of Tumor Necrosis Factor-α Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutations

Gowing¹,

Dequen²,

Soucy³

et al. 2006

J. Neurosci.

101

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An increase in the expression of the proinflammatory cytokine tumor necrosis factor ␣ (TNF-␣) has been observed in patients with amyotrophic lateral sclerosis (ALS) and in the mice models of the disease. TNF-␣ is a potent activator of macrophages and microglia and, under certain conditions, can induce or exacerbate neuronal cell death. Here, we assessed the contribution of TNF-␣ in motor neuron disease in mice overexpressing mutant superoxide dismutase 1 (SOD1) genes linked to familial ALS. This was accomplished by the generation of mice expressing SOD1 G37R or SOD1 G93A mutants in the context of TNF-␣ gene knock out. Surprisingly, the absence of TNF-␣ did not affect the lifespan or the extent of motor neuron loss in SOD1 transgenic mice. These results provide compelling evidence indicating that TNF-␣ does not directly contribute to motor neuron degeneration caused by SOD1 mutations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Absence of Tumor Necrosis Factor-α Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutations

Gowing¹,

Dequen²,

Soucy³

et al. 2006

J. Neurosci.

101

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“…Two highly relevant pro-inflammatory cytokines linked to the progression of disease in ALS include interleukin-1-beta (IL-1b) and tumor necrosis factor alpha (TNFa). Levels of these two pro-inflammatory cytokines are elevated in the blood and=or cerebrospinal fluid (CSF) of humans with ALS (33,111). Elevation of TNFa protein and mRNA are also observed in spinal cords from SOD1 G93A (59) and SOD1 G37R (101) ALS mice, and this correlates with enhanced NFkB activation (101).…”

Section: Nadph Oxidases Influence Disease Progression In a Sod1mentioning

confidence: 99%

Redox Modifier Genes and Pathways in Amyotrophic Lateral Sclerosis

Carter

Anklesaria

Choi

et al. 2009

Antioxidants & Redox Signaling

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Enhanced redox-stress caused by neuroinflammation, mitochondria, and NADPH oxidases has been hypothesized to play critical roles in disease progression of amyotrophic lateral sclerosis (ALS). However, distinguishing whether the redox-stress observed in ALS is due to a primary defect in cellular reactive oxygen species metabolism=catabolism, or is a secondary consequence of neuroinflammation, has been difficult and the issue remains a matter of debate. Emerging evidence suggests that defects in genes that regulate NADPH oxidases may account for at least some forms of ALS. NADPH oxidases are key signaling complexes that influence cellular responses to growth factors and cytokines. In this context, NADPH oxidase-derived reactive oxygen species exert spatial control over the redox-dependent activation of certain pro-inflammatory receptors. Understanding the biology of how NADPH oxidases control cell signaling may help to clarify how genetic determinants of ALS lead to dysregulated pro-inflammatory signaling. This review provides a framework for understanding endosomal signaling through NADPH oxidases and potential mechanisms whereby gene defects in various forms of ALS may influence this cellular process and lead to motor neuron degeneration. Lastly, this review discusses past and current efforts to treat ALS using antioxidant therapies, as well as the limitations and advantages of each of these approaches. Antioxid. Redox Signal. 11, 1569-1586.

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“…Initially perceived as a bystander effect, neuroinflammation is currently seen as beneficial at first, removing damaged cells and secreting supportive factors, and potentially detrimental thereafter by excessive release of cytokines (Beers et al, 2011a). Evidence of inflammation is detected in post mortem tissue (Schiffer et al, 1996;Anneser et al, 2004;Casula et al, 2011;Sta et al, 2011;Wang et al, 2011b), in cerebrospinal fluid (CSF) (Baron et al, 2005;Tateishi et al, 2010) and in blood samples of ALS patients (Poloni et al, 2000). In accordance, similar parameters of neuroinflammation are detected in ALS rodent models (among many others in Kiaei et al, 2006;Keller et al, 2009;Beers et al, 2011b).…”

Section: Neuroinflammation Observed In Alsmentioning

confidence: 80%