Insights into the Potential Role of Mercury in Alzheimer’s Disease

Bjørklund, Geir; Tinkov, Alexey A.; Dadar, Maryam; Rahman, Md. Mostafizur; Chirumbolo, Salvatore; Skalny, Anatoly V.; Skalnaya, Margarita G.; Haley, Boyd E.; Ajsuvakova, Olga P.; Aaseth, Jan

doi:10.1007/s12031-019-01274-3

Cited by 39 publications

(38 citation statements)

References 231 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mercury could conceivably affect AD pathology without directly interacting with the Aβ peptides themselves [90,94], for example, via toxic molecular mimicry [157], by promoting the aggregation of the tau fragment R2 [101] and phosphorylation of the tau protein as observed in SHSY5Y neuroblastoma cells [87], or via interactions between other forms of Aβ and Hg than those studied here. MeHg and Hg(II) ions bind to and affect the functions of important intracellular biomolecules with essential thiol (−SH) and selenohydryl (−SeH) groups, such as cysteine, homocysteine, metallothioneins, selenoproteins, glutathione (GSH), tubulin, ion channel proteins, transporters, metabolic enzymes, and N-methyl-D-aspartate (NMDA) receptors, thereby influencing or even damaging various tissues including nerve cells [94,97,153,157,158].…”

Section: Biological Relevance and Other Molecular Effects On Ad Involmentioning

confidence: 87%

“…The total inhibition of Aβ fibrillization at 1:1 Hg(II)/Aβ 40 ratio (Figures 1 and 2) shows that small amounts of mercury in a critical location can have a large impact on Aβ aggregation. As Hg poisoning correlates with a variety of adverse effects on developing neurites [153], neurotransmission [154], and cognitive function [97,155], the amount of Hg that enters the brain after exposure events clearly has biological impact [10,88,90,94]. While Hg(II) ions do not easily pass the blood-brain barrier (BBB), metallic vapor mercury does [100].…”

Section: Biological Relevance and Other Molecular Effects On Ad Involmentioning

confidence: 99%

See 1 more Smart Citation

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

et al. 2019

View full text Add to dashboard Cite

Brains and blood of Alzheimer’s disease (AD) patients have shown elevated mercury concentrations, but potential involvement of mercury exposure in AD pathogenesis has not been studied at the molecular level. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. Aβ peptide fibrillization is known to be modulated by metal ions such as Cu(II) and Zn(II). Here, we study in vitro the interactions between Aβ peptides and Hg(II) ions by multiple biophysical techniques. Fluorescence spectroscopy and atomic force microscopy (AFM) show that Hg(II) ions have a concentration-dependent inhibiting effect on Aβ fibrillization: at a 1:1 Aβ·Hg(II) ratio only non-fibrillar Aβ aggregates are formed. NMR spectroscopy shows that Hg(II) ions interact with the N-terminal region of Aβ(1–40) with a micromolar affinity, likely via a binding mode similar to that for Cu(II) and Zn(II) ions, i.e., mainly via the histidine residues His6, His13, and His14. Thus, together with Cu(II), Fe(II), Mn(II), Pb(IV), and Zn(II) ions, Hg(II) belongs to a family of metal ions that display residue-specific binding interactions with Aβ peptides and modulate their aggregation processes.

show abstract

Section: Biological Relevance and Other Molecular Effects On Ad Involmentioning

confidence: 87%

Section: Biological Relevance and Other Molecular Effects On Ad Involmentioning

confidence: 99%

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

et al. 2019

View full text Add to dashboard Cite

show abstract

“…They also reported that COX-derived prostanoids expressions reduces NO bioavailability, which might be responsible for the smooth functioning of blood vessels (Table 3) [121]. Rich scientific evidence is available that support the involvement of Hg in Alzheimer's diseases and also explain several associated insight like molecular mechanism including oxidative stress, Neuroinflammation, cholinergic and serotonergic transmission, amyloid plague formation, selenium depletion and epigenetic changes [122,123]. The high Hg contents were found in the Alzheimer's disease patients' brain regions and also in blood [124].…”

Section: Mercury (Hg)mentioning

confidence: 99%

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Patwa

Flora

2020

IJMS

View full text Add to dashboard Cite

Heavy metals are considered a continuous threat to humanity, as they cannot be eradicated. Prolonged exposure to heavy metals/metalloids in humans has been associated with several health risks, including neurodegeneration, vascular dysfunction, metabolic disorders, cancer, etc. Small blood vessels are highly vulnerable to heavy metals as they are directly exposed to the blood circulatory system, which has comparatively higher concentration of heavy metals than other organs. Cerebral small vessel disease (CSVD) is an umbrella term used to describe various pathological processes that affect the cerebral small blood vessels and is accepted as a primary contributor in associated disorders, such as dementia, cognitive disabilities, mood disorder, and ischemic, as well as a hemorrhagic stroke. In this review, we discuss the possible implication of heavy metals/metalloid exposure in CSVD and its associated disorders based on in-vitro, preclinical, and clinical evidences. We briefly discuss the CSVD, prevalence, epidemiology, and risk factors for development such as genetic, traditional, and environmental factors. Toxic effects of specific heavy metal/metalloid intoxication (As, Cd, Pb, Hg, and Cu) in the small vessel associated endothelium and vascular dysfunction too have been reviewed. An attempt has been made to highlight the possible molecular mechanism involved in the pathophysiology, such as oxidative stress, inflammatory pathway, matrix metalloproteinases (MMPs) expression, and amyloid angiopathy in the CSVD and related disorders. Finally, we discussed the role of cellular antioxidant defense enzymes to neutralize the toxic effect, and also highlighted the potential reversal strategies to combat heavy metal-induced vascular changes. In conclusion, heavy metals in small vessels are strongly associated with the development as well as the progression of CSVD. Chelation therapy may be an effective strategy to reduce the toxic metal load and the associated complications.

show abstract

“…According to the World Health Organization (11), the greatest source of mercury originates from the dental amalgam, which contains 50% mercury. Mercury vapor is continuously released from the amalgam in the non-ionized state [93] and then inhaled. It then enters the lungs, and 80% of the mercury is taken up by the blood.…”

Section: Discussionmentioning

confidence: 99%

A Hypothesis and Evidence That Mercury May be an Etiological Factor in Alzheimer’s Disease

Siblerud

Mutter

Moore

et al. 2019

IJERPH

View full text Add to dashboard Cite

Mercury is one of the most toxic elements and causes a multitude of health problems. It is ten times more toxic to neurons than lead. This study was created to determine if mercury could be causing Alzheimer’s disease (AD) by cross referencing the effects of mercury with 70 factors associated with AD. The results found that all these factors could be attributed to mercury. The hallmark changes in AD include plaques, beta amyloid protein, neurofibrillary tangles, phosphorylated tau protein, and memory loss—all changes that can be caused by mercury. Neurotransmitters such as acetylcholine, serotonin, dopamine, glutamate, and norepinephrine are inhibited in patients with Alzheimer’s disease, with the same inhibition occurring in mercury toxicity. Enzyme dysfunction in patients with Alzheimer’s disease include BACE 1, gamma secretase, cyclooxygenase-2, cytochrome-c-oxidase, protein kinases, monoamine oxidase, nitric oxide synthetase, acetyl choline transferase, and caspases, all which can be explained by mercury toxicity. Immune and inflammatory responses seen in patients with Alzheimer’s disease also occur when cells are exposed to mercury, including complement activation, cytokine expression, production of glial fibrillary acid protein antibodies and interleukin-1, transforming growth factor, beta 2 microglobulins, and phosphodiesterase 4 stimulation. Genetic factors in patients with Alzheimer’s disease are also associated with mercury. Apolipoprotein E 4 allele increases the toxicity of mercury. Mercury can inhibit DNA synthesis in the hippocampus, and has been associated with genetic mutations of presenilin 1 and 2, found in AD. The abnormalities of minerals and vitamins, specifically aluminum, calcium, copper, iron, magnesium, selenium, zinc, and vitamins B1, B12, E, and C, that occur in patients with Alzheimer’s disease, also occur in mercury toxicity. Aluminum has been found to increase mercury’s toxicity. Likewise, similar biochemical factors in AD are affected by mercury, including changes in blood levels of homocysteine, arachidonic acid, DHEA sulfate, glutathione, hydrogen peroxide, glycosamine glycans, acetyl-L carnitine, melatonin, and HDL. Other factors seen in Alzheimer’s disease, such as increased platelet activation, poor odor identification, hypertension, depression, increased incidences of herpes virus and chlamydia infections, also occur in mercury exposure. In addition, patients diagnosed with Alzheimer’s disease exhibit higher levels of brain mercury, blood mercury, and tissue mercury in some studies. The greatest exogenous sources of brain mercury come from dental amalgams. Conclusion: This review of the literature strongly suggests that mercury can be a cause of Alzheimer’s Disease.

show abstract

Insights into the Potential Role of Mercury in Alzheimer’s Disease

Cited by 39 publications

References 231 publications

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

A Hypothesis and Evidence That Mercury May be an Etiological Factor in Alzheimer’s Disease

Contact Info

Product

Resources

About