Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy
Abstract
1. Introduction
2. Pathologies Correlated with Metal Dyshomeostasis
2.1. Genetic Disorders
2.2. Acute and Chronic Metal Intoxication
2.3. Multifactorial Etiology
3. Exposure, Diagnosis, and Therapy of Metal-Related Diseases
3.1. Environmental Monitoring
3.2. Metal Accumulation Sites/Tissues
3.3. Drugs Enhancing/Involved in Metal Dyshomeostasis
3.4. Diagnosis
3.5. Therapy for Metal-Related Pathologies
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Metal | Disease | Gene | Affected Tissue | Therapy |
---|---|---|---|---|
Mn | Manganese transporter deficiency | SLC30A10 SLC39A14 (manganese transporter) | Liver, Nervous system | Manganese(II)-sulfate monohydrate [10] |
Fe | Aceruloplasminemia | CPL (Ceruloplasmin) CP (Ferroxidase) | Liver, pancreas, nervous system | Iron chelation (Deferoxamine, Deferasirox) + Vitamin E and C/+ Fresh Frozen Plasma, Zinc administration, Minocycline administration, Enzyme Replacement Therapy, Gene Therapy [11] |
Neuroferritinopathy, Hyperferritinemia-cataract syndrome, L-ferritin deficiency | FTL (iron storage) | Nervous system | Iron chelation (Deferoxamine, Deferasirox), dopamine-related drugs [12] | |
Spastic paraplegia type 35 | FA2H (fatty acid 2-hydroxylase (Synthesis of sphingolipids)) | Botulinum toxin injections, microtubule destabilizing drugs (e.g., vinblastine) [13] | ||
HARP syndrome (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration) | PANK2 (Pantothenate kinase (CoA synthesis)) | No therapy | ||
Pontocerebellar hypoplasia type 12 | COASY (CoA synthesis) | |||
Infantile neuroaxonal dystrophy 1, Neurodegeneration with brain iron accumulation 2B, Parkinson’s disease type 14 | PLA2G6 (Phospholipase) | |||
Spastic paraplegia 43, Neurodegeneration with brain iron accumulation 4 | C19orf12 (Mitochondrial magnesium homeostasis) | Intrathecal baclofen [14] | ||
Woodhouse–Sakati syndrome | DCAF17 (Ubiquitinylation) | Treatment is symptomatic (e.g., hormone replacement therapy for hypogonadism) [15] | ||
Neurodegeneration with brain iron accumulation type 5 | WDR45 (Autophagy) | Treatment is symptomatic [16] | ||
Kufor–Rakeb syndrome, Spastic paraplegia type 78 | ATP13A2 (Lysosomal divalent cation (transition metal) transporter) | Treatment is symptomatic [16] | ||
Hereditary hemochromatosis | HFE1 (HFE protein), HJV (Hemojuvelin), TrR2 (Trasferrin receptor-2), SLC40A1 (Ferroportin), HAMP (Hepcidin) | Liver, pancreas, heart | Therapeutic phlebotomy, iron chelating therapy, erythropoietin [17] | |
Cu | Wilson’s disease | ATP7B (beta polypeptide, ATPase, CuII transporting) | Liver, brain, kidneys, cornea | Copper chelation (e.g., Penicillamine, Trientine), zinc supplementation, Tetrathiomolybdate [18] |
MEDNIK syndrome | AP1S1 (adaptor protein complex 1 subunit β1) | liver, nervous system | Zinc supplementation (e.g., zinc acetate) [19] | |
Menkes Disease | ATP7A (ATPase Copper Transporting Alpha) | Nervous system, skeletal, skin | Copper supplementation (e.g., copper histidine) [20] | |
Occipital Horn Syndrome (OHS) | ATP7A (P-type ATPase) | Nervous system, skeletal, skin | Copper supplementation, disulfiram [21] | |
Huppke-Brendel Syndrome (HBS) | SLC33A1 | Nervous system | Treatment is symptomatic [22] | |
Zn | Acrodermatitis Enteropathica | SLC39A4 (Solute Carrier Family 39 Member 4) | Liver | Zinc supplementation [23] |
Transient Neonatal Zinc Deficiency | SLC30A2 (Solute carrier family 30 member 2) | Skin | Zinc replacement therapy [24] | |
Ehlers-Danlos Syndrome | SLC39A13 (zinc transporter ZIP13) | Nervous system, Muscle, skeletal | Nutritional supplements [25] | |
Birk-Landau-Perez Syndrome | SLC30A9 (Zinc transporter 9) | Nervous system, kidneys, | Symptomatic Therapy [26] | |
Se | Keshan Disease | Under investigation, genes related to selenoproteins and thioredoxin reductase | Heart | Selenium supplementation [27] |
Rigid spine muscular dystrophy 1 (RSMD1) and congenital myopathy with fiber-type disproportion | SEPN1 (Selenoprotein N) | Muscle nervous system | No approved drug therapies [28] |
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Lachowicz, J.I.; Lecca, L.I.; Meloni, F.; Campagna, M. Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy. Molecules 2021, 26, 6639. https://doi.org/10.3390/molecules26216639
Lachowicz JI, Lecca LI, Meloni F, Campagna M. Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy. Molecules. 2021; 26(21):6639. https://doi.org/10.3390/molecules26216639
Chicago/Turabian StyleLachowicz, Joanna Izabela, Luigi Isaia Lecca, Federico Meloni, and Marcello Campagna. 2021. "Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy" Molecules 26, no. 21: 6639. https://doi.org/10.3390/molecules26216639
APA StyleLachowicz, J. I., Lecca, L. I., Meloni, F., & Campagna, M. (2021). Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy. Molecules, 26(21), 6639. https://doi.org/10.3390/molecules26216639