TY  - JOUR
AU  - Bjørklund, Geir
AU  - Buha-Đorđević, Aleksandra
AU  - Hamdan, Halla
AU  - Wallace, David R.
AU  - Peana, Massimiliano
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5443
AB  - Autoimmunity is a multifaceted disorder influenced by both genetic and environmental factors, and metal exposure has been implicated as a potential catalyst, especially in autoimmune diseases affecting the central nervous system. Notably, metals like mercury, lead, and aluminum exhibit well-established neurotoxic effects, yet the precise mechanisms by which they elicit autoimmune responses in susceptible individuals remain unclear. Recent studies propose that metal-induced autoimmunity may arise from direct toxic effects on immune cells and tissues, coupled with indirect impacts on the gut microbiome and the blood-brain barrier. These effects can activate self-reactive T cells, prompting the production of autoantibodies, inflammatory responses, and tissue damage. Diagnosing metal-induced autoimmunity proves challenging due to nonspecific symptoms and a lack of reliable biomarkers. Treatment typically involves chelation therapy to eliminate excess metals and immunomodulatory agents to suppress autoimmune responses. Prevention strategies include lifestyle adjustments to reduce metal exposure and avoiding occupational and environmental risks. Prognosis is generally favorable with proper treatment; however, untreated cases may lead to autoimmune disorder progression and irreversible organ damage, particularly in the brain. Future research aims to identify genetic and environmental risk factors, enhance diagnostic precision, and explore novel treatment approaches for improved prevention and management of this intricate and debilitating disease.
PB  - Elsevier B.V.
T2  - Autoimmunity Reviews
T1  - Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions
VL  - 23
IS  - 3
DO  - 10.1016/j.autrev.2023.103509
DO  - 2-s2.0-85181822086
ER  - 

@article{
author = "Bjørklund, Geir and Buha-Đorđević, Aleksandra and Hamdan, Halla and Wallace, David R. and Peana, Massimiliano",
year = "2024",
abstract = "Autoimmunity is a multifaceted disorder influenced by both genetic and environmental factors, and metal exposure has been implicated as a potential catalyst, especially in autoimmune diseases affecting the central nervous system. Notably, metals like mercury, lead, and aluminum exhibit well-established neurotoxic effects, yet the precise mechanisms by which they elicit autoimmune responses in susceptible individuals remain unclear. Recent studies propose that metal-induced autoimmunity may arise from direct toxic effects on immune cells and tissues, coupled with indirect impacts on the gut microbiome and the blood-brain barrier. These effects can activate self-reactive T cells, prompting the production of autoantibodies, inflammatory responses, and tissue damage. Diagnosing metal-induced autoimmunity proves challenging due to nonspecific symptoms and a lack of reliable biomarkers. Treatment typically involves chelation therapy to eliminate excess metals and immunomodulatory agents to suppress autoimmune responses. Prevention strategies include lifestyle adjustments to reduce metal exposure and avoiding occupational and environmental risks. Prognosis is generally favorable with proper treatment; however, untreated cases may lead to autoimmune disorder progression and irreversible organ damage, particularly in the brain. Future research aims to identify genetic and environmental risk factors, enhance diagnostic precision, and explore novel treatment approaches for improved prevention and management of this intricate and debilitating disease.",
publisher = "Elsevier B.V.",
journal = "Autoimmunity Reviews",
title = "Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions",
volume = "23",
number = "3",
doi = "10.1016/j.autrev.2023.103509, 2-s2.0-85181822086"
}

Bjørklund, G., Buha-Đorđević, A., Hamdan, H., Wallace, D. R.,& Peana, M.. (2024). Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions. in Autoimmunity Reviews
Elsevier B.V.., 23(3).
https://doi.org/10.1016/j.autrev.2023.103509

Bjørklund G, Buha-Đorđević A, Hamdan H, Wallace DR, Peana M. Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions. in Autoimmunity Reviews. 2024;23(3).
doi:10.1016/j.autrev.2023.103509 .

Bjørklund, Geir, Buha-Đorđević, Aleksandra, Hamdan, Halla, Wallace, David R., Peana, Massimiliano, "Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions" in Autoimmunity Reviews, 23, no. 3 (2024),
https://doi.org/10.1016/j.autrev.2023.103509 . .

TY  - JOUR
AU  - Nurchi, Valeria M.
AU  - Buha-Đorđević, Aleksandra
AU  - Crisponi, Guido
AU  - Alexander, Jan
AU  - Bjørklund, Geir
AU  - Aaseth, Jan
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3518
AB  - High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.
PB  - MDPI AG
T2  - Biomolecules
T1  - Arsenic toxicity: Molecular targets and therapeutic agents
VL  - 10
IS  - 2
DO  - 10.3390/biom10020235
ER  - 

@article{
author = "Nurchi, Valeria M. and Buha-Đorđević, Aleksandra and Crisponi, Guido and Alexander, Jan and Bjørklund, Geir and Aaseth, Jan",
year = "2020",
abstract = "High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.",
publisher = "MDPI AG",
journal = "Biomolecules",
title = "Arsenic toxicity: Molecular targets and therapeutic agents",
volume = "10",
number = "2",
doi = "10.3390/biom10020235"
}

Nurchi, V. M., Buha-Đorđević, A., Crisponi, G., Alexander, J., Bjørklund, G.,& Aaseth, J.. (2020). Arsenic toxicity: Molecular targets and therapeutic agents. in Biomolecules
MDPI AG., 10(2).
https://doi.org/10.3390/biom10020235

Nurchi VM, Buha-Đorđević A, Crisponi G, Alexander J, Bjørklund G, Aaseth J. Arsenic toxicity: Molecular targets and therapeutic agents. in Biomolecules. 2020;10(2).
doi:10.3390/biom10020235 .

Nurchi, Valeria M., Buha-Đorđević, Aleksandra, Crisponi, Guido, Alexander, Jan, Bjørklund, Geir, Aaseth, Jan, "Arsenic toxicity: Molecular targets and therapeutic agents" in Biomolecules, 10, no. 2 (2020),
https://doi.org/10.3390/biom10020235 . .

TY  - JOUR
AU  - Aaseth, Jan
AU  - Buha, Aleksandra
AU  - Wallace, David R.
AU  - Bjørklund, Geir
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3544
AB  - Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies.
PB  - MDPI
T2  - International Journal of Environmental Research and Public Health
T1  - Xenobiotics, trace metals and genetics in the pathogenesis of tauopathies
VL  - 17
IS  - 4
DO  - 10.3390/ijerph17041269
ER  - 

@article{
author = "Aaseth, Jan and Buha, Aleksandra and Wallace, David R. and Bjørklund, Geir",
year = "2020",
abstract = "Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies.",
publisher = "MDPI",
journal = "International Journal of Environmental Research and Public Health",
title = "Xenobiotics, trace metals and genetics in the pathogenesis of tauopathies",
volume = "17",
number = "4",
doi = "10.3390/ijerph17041269"
}

Aaseth, J., Buha, A., Wallace, D. R.,& Bjørklund, G.. (2020). Xenobiotics, trace metals and genetics in the pathogenesis of tauopathies. in International Journal of Environmental Research and Public Health
MDPI., 17(4).
https://doi.org/10.3390/ijerph17041269

Aaseth J, Buha A, Wallace DR, Bjørklund G. Xenobiotics, trace metals and genetics in the pathogenesis of tauopathies. in International Journal of Environmental Research and Public Health. 2020;17(4).
doi:10.3390/ijerph17041269 .

Aaseth, Jan, Buha, Aleksandra, Wallace, David R., Bjørklund, Geir, "Xenobiotics, trace metals and genetics in the pathogenesis of tauopathies" in International Journal of Environmental Research and Public Health, 17, no. 4 (2020),
https://doi.org/10.3390/ijerph17041269 . .

TY  - JOUR
AU  - Bjørklund, Geir
AU  - Crisponi, Guido
AU  - Nurchi, Valeria Marina
AU  - Cappai, Rosita
AU  - Buha-Đorđević, Aleksandra
AU  - Aaseth, Jan
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3460
AB  - The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.
PB  - MDPI
T2  - Molecules
T1  - A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead
VL  - 24
IS  - 3247
SP  - 1
EP  - 32
DO  - 10.3390/molecules24183247
ER  - 

@article{
author = "Bjørklund, Geir and Crisponi, Guido and Nurchi, Valeria Marina and Cappai, Rosita and Buha-Đorđević, Aleksandra and Aaseth, Jan",
year = "2019",
abstract = "The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.",
publisher = "MDPI",
journal = "Molecules",
title = "A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead",
volume = "24",
number = "3247",
pages = "1-32",
doi = "10.3390/molecules24183247"
}

Bjørklund, G., Crisponi, G., Nurchi, V. M., Cappai, R., Buha-Đorđević, A.,& Aaseth, J.. (2019). A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead. in Molecules
MDPI., 24(3247), 1-32.
https://doi.org/10.3390/molecules24183247

Bjørklund G, Crisponi G, Nurchi VM, Cappai R, Buha-Đorđević A, Aaseth J. A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead. in Molecules. 2019;24(3247):1-32.
doi:10.3390/molecules24183247 .

Bjørklund, Geir, Crisponi, Guido, Nurchi, Valeria Marina, Cappai, Rosita, Buha-Đorđević, Aleksandra, Aaseth, Jan, "A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead" in Molecules, 24, no. 3247 (2019):1-32,
https://doi.org/10.3390/molecules24183247 . .