The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans

Estevez, Annette O.; Morgan, Kathleen L.; Szewczyk, Nathaniel J.; Gems, David; Estevez, Miguel

doi:10.1016/j.neuro.2013.12.012

Cited by 45 publications

(22 citation statements)

References 112 publications

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“…The strongest evidence of Se neurotoxicity indicates a selective damage to motor neurons favoring the onset of the human motor neuron disease ALS, first related to environmental Se following the observation of a cluster of this disease in a seleniferous area of South Dakota [14]. The plausibility of such associations has been strongly supported by several veterinary medicine investigations, which have reported a selective damage of motor neurons in Se-intoxicated pigs, and by some alternations in laboratory studies supporting an etiologic role in the human disease [14,50,51]. In addition to such possible involvement in ALS etiology, some evidence suggests developmental neurotoxicity of Se as assessed through visual evoked potentials [52], or an excess occurrence of lethargy, dizziness, motor weakness and paresthesias [14], though not all the results are consistent and therefore convincing evidence is still lacking.…”

Section: Accepted Manuscriptmentioning

confidence: 97%

Selenium and Human Health: Witnessing a Copernican Revolution?

Jabłońska

Vinceti

2015

Journal of Environmental Science and Health, Part C

140

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In humans, selenium was hypothesized to lower the risk of several chronic diseases, mainly due to the antioxidant activity of selenium-containing proteins. Recent epidemiologic and laboratory Downloaded by [New York University] at 16:24 19 June 2015 ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT 2studies, however, are changing our perception of the biological effects of this nutritionally essential trace element. We reviewed the most recent epidemiologic and biochemical literature on selenium, synthesizing the findings from these studies into a unifying view. Randomized trials have shown that selenium did not protect against cancer and other chronic diseases, but even increased the risk of specific neoplasms such as advanced prostate cancer and skin cancer, in addition to type 2 diabetes. Biochemical studies indicate that selenium may exert a broad pattern of toxic effects at unexpectedly low concentrations. Furthermore, its upregulation of antioxidant proteins (selenium-dependent and selenium-independent) may be a manifestation of self-induced oxidative stress. In conclusion, toxic effects of selenium species occur at lower concentrations than previously believed. Those effects may include a large range of proteomic changes and adverse health effects in humans. Since the effects of environmental exposure to this element on human health still remain partially unknown, but are potentially serious, the toxicity of selenium exposure should be further investigated and considered as a public health priority.

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Section: Accepted Manuscriptmentioning

confidence: 97%

Selenium and Human Health: Witnessing a Copernican Revolution?

Jabłońska

Vinceti

2015

Journal of Environmental Science and Health, Part C

140

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“…185 Selenite induced degeneration of cholinergic and GABAergic neurons and impaired locomotor activity in Caenorhabditis elegans. [186][187][188] The elevated SeO 3 2À in CSF of ALS patients may be due to excessive exposure to this compound from environmental sources, alteration of the body's detoxification capacity or even genetic modifications. Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by increased repetition of CAG trinucleotide in exon 1 of the Huntington gene, resulting in polyQ-expanded sequence in N-terminal region of the Huntington protein.…”

Section: Other Neurodegenerative Diseasesmentioning

confidence: 99%

Selenium, selenoproteins and neurodegenerative diseases

et al. 2015

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It is unsurprising that our understanding of the role of selenium in neurological function is somewhat immature, considering its relatively recent discovery as an essential element to human health. Selenocysteine, the 21st amino acid, is the defining feature of the 25 selenoprotein-encoding genes so far discovered within the human genome. The low abundance of these proteins in the brain belies the integral role they play in normal neurological function, from well-characterised antioxidant activity in the periphery to poorly understood mechanisms that modulate mitochondrial function and response to brain pathology. Selenium has been identified as playing a role in several neurodegenerative disorders, including Alzheimer's and Parkinson's disease, though its function as a 'cause or effect' of disease process remains unclear. This review discusses selenium metabolism in detail, specifically with regard to the role it plays within the central nervous system, and examines the most current literature investigating how selenium may be involved in chronic diseases of the central nervous system.

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“…As a result, numerous therapeutic strategies are under development for neurodegenerative disease. These include therapies directed against oxidative stress (20, 24, 26–34), exposure to metal toxicity (35–39), loss of sirtuin activity (4, 7, 40–48), poly(ADP-ribose) polymerase-1 (PARP-1) over-activation (49–59), decreased metabotropic glutamate activity (60–72), cellular metabolic dysfunction (19, 28, 73–78), defects in gamma-aminobutyric acid (GABA) signaling (79–83), transcription factor activation (4, 47, 80, 84–99), Src homology-2 (SH2) domain phosphorylation (100–107), components of the mechanistic target of rapamycin (mTOR) pathway (7, 16, 108–120), and growth factors (119, 121–125). …”

Section: The Growth Factor and Cytokine Erythropoietinmentioning

confidence: 99%

Regeneration in the nervous system with erythropoietin

Maiese¹

2016

Front Biosci

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Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system.

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The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans

Cited by 45 publications

References 112 publications

Selenium and Human Health: Witnessing a Copernican Revolution?

Selenium and Human Health: Witnessing a Copernican Revolution?

Selenium, selenoproteins and neurodegenerative diseases

Regeneration in the nervous system with erythropoietin

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