Abnormal Serum Iron-Status Indicator Changes in Amyotrophic Lateral Sclerosis (ALS) Patients: A Meta-Analysis

Wang, Lan; Li, Chunyu; Chen, Xueping; Li, Shuying; Shang, Huifang

doi:10.3389/fneur.2020.00380

Cited by 17 publications

(15 citation statements)

References 45 publications

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“…Further studies are needed to address these questions. The difference between the current meta-analysis and the previous one [ 83 ] was that we conducted a more comprehensive literature search that included more studies, with some inconsistent results, and that we analyzed the association between ALS patients and survival time and found a negative correlation between ferritin level and the overall survival.…”

Section: Discussionmentioning

confidence: 99%

Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Cheng

Chen

Shang

2021

Transl Neurodegener

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Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06–0.21], p = 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12–78.73], p < 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52–4.05], p < 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90–127.67], p < 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = − 2.42, 95% CI [− 3.93, − 0.90], p = 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02–1.88], p = 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.

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Section: Discussionmentioning

confidence: 99%

Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Cheng

Chen

Shang

2021

Transl Neurodegener

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“…Although the pathological hallmarks of neurodegenerative diseases such as PD, AD, ALS, and MS differ significantly, they all share some common factors: in addition to the already described inflammation and oxidative stress, increased iron levels in specific areas of the brain and cerebrospinal fluid [100] have been reported [72,[101][102][103]. Indeed, possible dysfunctions of iron metabolism in the CNS have recently turned out to be one of the pivotal points upon which extensive research for pathological mechanisms in neurodegenerative diseases has been focused.…”

Section: Dmf As Regulator Of Iron Metabolism For the Treatment Of Neumentioning

confidence: 99%

Exploring the Use of Dimethyl Fumarate as Microglia Modulator for Neurodegenerative Diseases Treatment

et al. 2020

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The maintenance of redox homeostasis in the brain is critical for the prevention of the development of neurodegenerative diseases. Drugs acting on brain redox balance can be promising for the treatment of neurodegeneration. For more than four decades, dimethyl fumarate (DMF) and other derivatives of fumaric acid ester compounds have been shown to mitigate a number of pathological mechanisms associated with psoriasis and relapsing forms of multiple sclerosis (MS). Recently, DMF has been shown to exert a neuroprotective effect on the central nervous system (CNS), possibly through the modulation of microglia detrimental actions, observed also in multiple brain injuries. In addition to the hypothesis that DMF is linked to the activation of NRF2 and NF-kB transcription factors, the neuroprotective action of DMF may be mediated by the activation of the glutathione (GSH) antioxidant pathway and the regulation of brain iron homeostasis. This review will focus on the role of DMF as an antioxidant modulator in microglia processes and on its mechanisms of action in the modulation of different pathways to attenuate neurodegenerative disease progression.

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“…Iron dysregulation is emerging as a key phenotype in the pathogenesis of ALS [ 52 ]. A new meta-analysis by Lang W. and coworkers suggests that ALS patients display no difference in total iron pool relative to control healthy patients [ 53 ]. In contrast, there is a staggering difference in the levels of ferritin and transferrin.…”

Section: Discussionmentioning

confidence: 99%

A Synthetic SOD/Catalase Mimic Compound for the Treatment of ALS

et al. 2021

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. To date, the etiology of the disease is still unclear, with evidence of reactive oxygen species, mitochondrial dysfunction, iron homeostasis perturbation, protein misfolding and protein aggregation as key players in the pathology of the disease. Twenty percent of familial ALS and two percent of sporadic ALS instances are due to a mutation in Cu/Zn superoxide dismutase (SOD1). Sporadic and familial ALS affects the same neurons with similar pathology; therefore, the underlying hypothesis is that therapies effective in mutant SOD1 models could be translated to sporadic ALS. Corrole metal complexes have lately been identified as strong and potent catalytic antioxidants with beneficial effects in oxidative stress-related diseases such as Parkinson’s disease, Alzheimer’s disease, atherosclerosis, diabetes and its complications. One of the most promising candidates is the iron complex of an amphiphilic corrole, 1-Fe. In this study we used the SOD1 G93R mutant zebrafish ALS model to assess whether 1-Fe, as a potent catalytic antioxidant, displays any therapeutic merits in vivo. Our results show that 1-Fe caused a substantial increase in mutant zebrafish locomotor activity (up to 30%), bringing the locomotive abilities of the mutant treated group close to that of the wild type untreated group (50% more than the mutated untreated group). Furthermore, 1-Fe did not affect WT larvae locomotor activity, suggesting that 1-Fe enhances locomotor ability by targeting mechanisms underlying SOD1 ALS specifically. These results may pave the way for future development of 1-Fe as a viable treatment for ALS.

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Abnormal Serum Iron-Status Indicator Changes in Amyotrophic Lateral Sclerosis (ALS) Patients: A Meta-Analysis

Cited by 17 publications

References 45 publications

Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Exploring the Use of Dimethyl Fumarate as Microglia Modulator for Neurodegenerative Diseases Treatment

A Synthetic SOD/Catalase Mimic Compound for the Treatment of ALS

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