Lead, cadmium, and selenium in the blood of patients with sporadic amyotrophic lateral sclerosis

Vinceti, Marco; Guidetti, Donata; Bergomi, Margherita; Caselgrandi, Eva; Vivoli, Roberto; Olmi, M.; Rinaldi, L; Rovesti, Sergio; Solimé, F

doi:10.1007/bf01999568

Cited by 59 publications

(40 citation statements)

References 31 publications

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“…Consistent with previous data, Vinceti et al [17] found no abnormalities in whole blood lead levels during early stages of the disease. However, they noted a positive correlation between whole blood lead levels and the progression of the disease, measured in this case by worsening functional impairment.…”

Section: Leadsupporting

confidence: 82%

The Association of Exposure to Lead, Mercury, and Selenium and the Development of Amyotrophic Lateral Sclerosis and the Epigenetic Implications

et al. 2010

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Metal exposures are an intriguing potential culprit in the cause of sporadic amyotrophic lateral sclerosis (ALS). For one, there are numerous case reports linking different metals to an ALS phenotype. Furthermore, some investigators have demonstrated higher levels of certain metals in the blood, bone, cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to controls. There are also many case-control studies looking at the possible association of certain metals with the development of ALS. We have reviewed the relevant literature regarding metal exposures and the risk of developing ALS. We found that many different metals have been implicated as having a role in ALS, but there is more literature investigating the role of lead than any other metal. Despite many studies, the role, if any, of this metal in the pathogenesis of ALS remains unclear. Similarly, other metals either have inconclusive, conflicting, or insufficient results in order to make a definitive conclusion. One explanation for these findings is that metal exposures alone are insufficient for the development of ALS. Perhaps an interaction between the metal exposure and an individual’s genetic makeup is required to produce epigenetic changes that ultimately lead to ALS.

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Section: Leadsupporting

confidence: 82%

The Association of Exposure to Lead, Mercury, and Selenium and the Development of Amyotrophic Lateral Sclerosis and the Epigenetic Implications

et al. 2010

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“…Among the metals analyzed, Pb resulted higher in patients' than in controls' group. Much evidence in the literature describes Pb as a neurotoxic agent and as being related to ALS [22,23], since high levels of this metal have been found both in blood and in cerebrospinal fluid of ALS patients [24,25]. In our analyses, Pb levels were twice higher in ALS subjects than in controls, supporting the hypothesis of a possible involvement of this metal in the etiology of the disease.…”

Section: Discussionsupporting

confidence: 82%

Serum metal evaluation in a small cohort of Amyotrophic Lateral Sclerosis patients reveals high levels of thiophylic species

Benedetti¹,

Lucchini²,

Marocchi³

et al. 2016

Peptidomics

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Amyotrophic Lateral Sclerosis (ALS) has often been associated with improper/altered metal metabolism. Analysis of thiophylic metals in serum from a small and geographically restricted cohort of ALS patients indicates contents of Pb and Ni much higher in patients than in controls (Ni, 5-fold; Pb, 2-fold). Se levels are also higher in the patients’ group, which has instead lower As levels than controls. Thiophylic metals may impair biogenesis of FeS clusters or substitute for iron, even in folded proteins; Se may non-functionally replace S. Thus, improper assembly/ function of FeS proteins could represent another possible issue to be considered in ALS pathogenesis.

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“…For instance, Wistar rats developed peripheral polyneuropathy after long-term exposure to Cd 2+ from drinking water (Sato et al, 1978). In humans, Cd 2+ concentrations are significantly elevated in the brains of AD (Lui et al, 1990) and ALS (Vinceti et al, 1997) patients. Also, occupational exposure to Cd 2+ increases the risk of AD (Bar-Sela et al, 2001), ALS, and brain atrophy (Bar-Sela et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

The heavy metal cadmium induces valosin-containing protein (VCP)-mediated aggresome formation

Song

Xiao

Nagashima

et al. 2008

Toxicology and Applied Pharmacology

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Cadmium (Cd 2+ ) is a heavy metal ion known to have a long biological half-life in humans. Accumulating evidence shows that exposure to Cd 2+ is associated with neurodegenerative diseases characterized by the retention of ubiquitinated and misfolded proteins in the lesions. Here, we report that Cd 2+ directly induces the formation of protein inclusion bodies in cells. The protein inclusion body is an aggresome, a major organelle for collecting ubiquitinated or misfolded proteins. Our results show that aggresomes are enriched in the detergent-insoluble fraction of Cd 2+ -treated cell lysates. Proteomic analysis identified 145 proteins in the aggresome-enriched fractions. One of the proteins is the highly conserved valosin-containing protein (VCP), which has been shown to colocalize with aggresomes and bind ubiquitinated proteins through its N domain (#1-200). Our subsequent examination of VCP's role in the formation of aggresomes induced by Cd 2+ indicate that the C-terminal tail (#780-806) of VCP interacts with histone deacetylase HDAC6, a mediator for aggresome formation, suggesting that VCP participates in transporting ubiquitinated proteins to aggresomes. This function of VCP is impaired by inhibition of the deacetylase activity of HDAC6 or by over-expression of VCP mutants that do not bind ubiquitinated proteins or HDAC6. Our results indicate that Cd 2+ induces the formation of protein inclusion bodies by promoting the accumulation of ubiquitinated proteins in aggresomes through VCP and HDAC6. Our delineation of the role of VCP in regulating cell responses to ubiquitinated proteins has important implications for understanding Cd 2+ toxicity and associated diseases.

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Lead, cadmium, and selenium in the blood of patients with sporadic amyotrophic lateral sclerosis

Cited by 59 publications

References 31 publications

The Association of Exposure to Lead, Mercury, and Selenium and the Development of Amyotrophic Lateral Sclerosis and the Epigenetic Implications

The Association of Exposure to Lead, Mercury, and Selenium and the Development of Amyotrophic Lateral Sclerosis and the Epigenetic Implications

Serum metal evaluation in a small cohort of Amyotrophic Lateral Sclerosis patients reveals high levels of thiophylic species

The heavy metal cadmium induces valosin-containing protein (VCP)-mediated aggresome formation

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