Amyotrophic lateral sclerosis and lead: A systematic update

Farace, Cristiano; Fenu, Grazia; Lintas, Simone; Oggiano, Riccardo; Pisano, Andrea; Sabalic, Angela; Solinas, Giuliana; Bocca, Beatrice; Forte, Giovanni; Madeddu, Roberto

doi:10.1016/j.neuro.2020.09.003

Cited by 24 publications

(17 citation statements)

References 54 publications

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“…In an animal model, similarly, chronic exposure to PM resulted in a dose-dependent increase in pure cortical neuronal loss and selective neuronal loss especially of the motor cortex, primary somatosensory cortex, and piriform cortex [60]. In addition, traffic-related pollution may contain elements characterized by neurotoxic effects, especially heavy metals such as lead, cadmium, mercury, and selenium already associated with ALS risk [61][62][63][64][65][66]. A neuroimaging study showed that long-term exposure to high ambient air pollution may lead to cortical thinning and reduced subcortical volume in adults [67].…”

Section: Discussionmentioning

confidence: 99%

Risk of Amyotrophic Lateral Sclerosis and Exposure to Particulate Matter from Vehicular Traffic: A Case-Control Study

Filippini

Mandrioli

Malagoli

et al. 2021

IJERPH

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(1) Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with still unknown etiology. Some occupational and environmental risk factors have been suggested, including long-term air pollutant exposure. We carried out a pilot case-control study in order to evaluate ALS risk due to particulate matter with a diameter of ≤10 µm (PM10) as a proxy of vehicular traffic exposure. (2) Methods: We recruited ALS patients and controls referred to the Modena Neurology ALS Care Center between 1994 and 2015. Using a geographical information system, we modeled PM10 concentrations due to traffic emissions at the geocoded residence address at the date of case diagnosis. We computed the odds ratio (OR) and 95% confidence interval (CI) of ALS according to increasing PM10 exposure, using an unconditional logistic regression model adjusted for age and sex. (3) Results: For the 132 study participants (52 cases and 80 controls), the average of annual median and maximum PM10 concentrations were 5.2 and 38.6 µg/m3, respectively. Using fixed cutpoints at 5, 10, and 20 of the annual median PM10 levels, and compared with exposure <5 µg/m3, we found no excess ALS risk at 5–10 µg/m3 (OR 0.87, 95% CI 0.39–1.96), 10–20 µg/m3 (0.94, 95% CI 0.24–3.70), and ≥20 µg/m3 (0.87, 95% CI 0.05–15.01). Based on maximum PM10 concentrations, we found a statistically unstable excess ALS risk for subjects exposed at 10–20 µg/m3 (OR 4.27, 95% CI 0.69–26.51) compared with those exposed <10 µg/m3. However, risk decreased at 20–50 µg/m3 (OR 1.49, 95% CI 0.39–5.75) and ≥50 µg/m3 (1.16, 95% CI 0.28–4.82). ALS risk in increasing tertiles of exposure showed a similar null association, while comparison between the highest and the three lowest quartiles lumped together showed little evidence for an excess risk at PM10 concentrations (OR 1.13, 95% CI 0.50–2.55). After restricting the analysis to subjects with stable residence, we found substantially similar results. (4) Conclusions: In this pilot study, we found limited evidence of an increased ALS risk due to long-term exposure at high PM10 concentration, though the high statistical imprecision of the risk estimates, due to the small sample size, particularly in some exposure categories, limited our capacity to detect small increases in risk, and further larger studies are needed to assess this relation.

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Section: Discussionmentioning

confidence: 99%

Risk of Amyotrophic Lateral Sclerosis and Exposure to Particulate Matter from Vehicular Traffic: A Case-Control Study

Filippini

Mandrioli

Malagoli

et al. 2021

IJERPH

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“…Mutations in a series of RNA-binding protein (RBP) genes (TDP-43, FUS, hnRNPA1, ATXN2, TIA-1) have been confirmed to cause ALS and/or FTD. [15][16][17] Most of the diseasecausing mutations map to the low complexity domain regions of SG-related RBPs and disrupt their biophysical properties, leading to increased LLPS (liquid-liquid phase separation) into SGs and aggregate formation. 18 The LLPS of UBQLN2 under certain environmental conditions is similar to that of RNP particles.…”

Section: Introductionmentioning

confidence: 99%

Amyotrophic lateral sclerosis (ALS) linked mutation in Ubiquilin 2 affects stress granule assembly via TIA‐1

Peng

Niu

et al. 2021

CNS Neurosci Ther

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“…Advanced age (between 55 and 65 years) is an established risk factor, though fALS is generally related to a younger age of onset. Male gender, smoking, physical stress, exposure to heavy metals, persistent pollutants and environmental toxins such as β-methylamino-L-alanine, which is why people in Guam were susceptible to ALS with higher prevalence [ 10 , 11 ], are other risk factors that trigger sALS [ 12 , 13 , 14 ]. However, the genetic background, the etiology and the exact mechanisms of sALS are not yet known.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis

Sever

Çi̇ftçi̇

DeMi̇rci̇

et al. 2022

IJMS

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Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS.

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Amyotrophic lateral sclerosis and lead: A systematic update

Cited by 24 publications

References 54 publications

Risk of Amyotrophic Lateral Sclerosis and Exposure to Particulate Matter from Vehicular Traffic: A Case-Control Study

Risk of Amyotrophic Lateral Sclerosis and Exposure to Particulate Matter from Vehicular Traffic: A Case-Control Study

Amyotrophic lateral sclerosis (ALS) linked mutation in Ubiquilin 2 affects stress granule assembly via TIA‐1

Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis

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