{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:33:01Z","timestamp":1788849181947,"version":"build-2803163510"},"reference-count":156,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAAA","award":["R03 AA022479"],"award-info":[{"award-number":["R03 AA022479"]}]},{"name":"NIH\/NIAAA","award":["2 SO6 GM08016-39"],"award-info":[{"award-number":["2 SO6 GM08016-39"]}]},{"name":"NIH\/NIAAA","award":["R01ES10563"],"award-info":[{"award-number":["R01ES10563"]}]},{"name":"NIH\/NIAAA","award":["R01ES07331"],"award-info":[{"award-number":["R01ES07331"]}]},{"name":"NIH\/NIGMS","award":["R03 AA022479"],"award-info":[{"award-number":["R03 AA022479"]}]},{"name":"NIH\/NIGMS","award":["2 SO6 GM08016-39"],"award-info":[{"award-number":["2 SO6 GM08016-39"]}]},{"name":"NIH\/NIGMS","award":["R01ES10563"],"award-info":[{"award-number":["R01ES10563"]}]},{"name":"NIH\/NIGMS","award":["R01ES07331"],"award-info":[{"award-number":["R01ES07331"]}]},{"name":"National Institute of Environmental Health Sciences (NIEHS)","award":["R03 AA022479"],"award-info":[{"award-number":["R03 AA022479"]}]},{"name":"National Institute of Environmental Health Sciences (NIEHS)","award":["2 SO6 GM08016-39"],"award-info":[{"award-number":["2 SO6 GM08016-39"]}]},{"name":"National Institute of Environmental Health Sciences (NIEHS)","award":["R01ES10563"],"award-info":[{"award-number":["R01ES10563"]}]},{"name":"National Institute of Environmental Health Sciences (NIEHS)","award":["R01ES07331"],"award-info":[{"award-number":["R01ES07331"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since the HTT protein is involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to the disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations; however, at higher concentrations, they can exacerbate HD by disrupting glial\u2013neuronal communication and\/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese, and copper with glial\u2013neuron communication and GM and indicate how this knowledge may pave the way for the development of a new generation of disease-modifying therapies in HD.<\/jats:p>","DOI":"10.3390\/cells13131144","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T12:28:48Z","timestamp":1720009728000},"page":"1144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1703-1842","authenticated-orcid":false,"given":"Yousef","family":"Tizabi","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5800-1044","authenticated-orcid":false,"given":"Samia","family":"Bennani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy of Casablanca, Hassan II University, Casablanca 20670, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nacer","family":"El Kouhen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy of Casablanca, Hassan II University, Casablanca 20670, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3523-2154","authenticated-orcid":false,"given":"Bruk","family":"Getachew","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2619-1656","authenticated-orcid":false,"given":"Michael","family":"Aschner","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref_1","unstructured":"Ajitkumar, A., and De Jesus, O. (2024). Huntington Disease, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.4103\/1673-5374.390969","article-title":"Therapeutic Advances in Neural Regeneration for Huntington\u2019s Disease","volume":"19","author":"Castelli","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Heemskerk, A.-W., and Roos, R.A.C. (2012). Aspiration Pneumonia and Death in Huntington\u2019s Disease. PLoS Curr., 4.","DOI":"10.1371\/currents.RRN1293"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Finkbeiner, S. (2011). Huntington\u2019s Disease. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a007476"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000443738","article-title":"The Prevalence of Huntington\u2019s Disease","volume":"46","author":"Rawlins","year":"2016","journal-title":"Neuroepidemiology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Barron, J.C., Hurley, E.P., and Parsons, M.P. (2021). Huntingtin and the Synapse. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.689332"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, A., Lalonde, K., Truesdell, A., Gomes Welter, P., Brocardo, P.S., Rosenstock, T.R., and Gil-Mohapel, J. (2021). New Avenues for the Treatment of Huntington\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168363"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Khoshnan, A. (2024). Gut Microbiota as a Modifier of Huntington\u2019s Disease Pathogenesis. J. Huntingt. Dis., online ahead of print.","DOI":"10.3233\/JHD-240012"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"baad060","DOI":"10.1093\/database\/baad060","article-title":"PolyQ Database\u2014An Integrated Database on Polyglutamine Diseases","volume":"2023","author":"Estevam","year":"2023","journal-title":"Database"},{"key":"ref_10","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J., Gripp, K.W., and Amemiya, A. (1993). Huntington Disease. GeneReviews\u00ae, University of Washington."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3233\/JHD-200394","article-title":"The Neurodevelopmental Hypothesis of Huntington\u2019s Disease","volume":"9","author":"Schultz","year":"2020","journal-title":"J. Huntingt. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.it.2015.04.007","article-title":"The Choreography of Neuroinflammation in Huntington\u2019s Disease","volume":"36","author":"Crotti","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Palpagama, T.H., Waldvogel, H.J., Faull, R.L.M., and Kwakowsky, A. (2019). The Role of Microglia and Astrocytes in Huntington\u2019s Disease. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00258"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Donley, D.W., Realing, M., Gigley, J.P., and Fox, J.H. (2021). Iron Activates Microglia and Directly Stimulates Indoleamine-2,3-Dioxygenase Activity in the N171-82Q Mouse Model of Huntington\u2019s Disease. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250606"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lobato, A.G., Ortiz-Vega, N., Zhu, Y., Neupane, D., Meier, K.K., and Zhai, R.G. (2024). Copper Enhances Aggregational Toxicity of Mutant Huntingtin in a Drosophila Model of Huntington\u2019s Disease. Biochim. Biophys. Acta BBA-Mol. Basis Dis., 1870.","DOI":"10.1016\/j.bbadis.2023.166928"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11795735221092517","DOI":"10.1177\/11795735221092517","article-title":"Current and Possible Future Therapeutic Options for Huntington\u2019s Disease","volume":"14","author":"Ferguson","year":"2022","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"ref_17","first-page":"545","article-title":"Tetrabenazine in the Treatment of Huntington\u2019s Disease","volume":"3","author":"Paleacu","year":"2007","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41587-021-00955-y","article-title":"Questions Swirl around Failures of Disease-Modifying Huntington\u2019s Drugs","volume":"39","author":"Sheridan","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1007\/s12035-022-03150-5","article-title":"CRISPR\/Cas9 Mediated Therapeutic Approach in Huntington\u2019s Disease","volume":"60","author":"Alkanli","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S1474-4422(22)00121-1","article-title":"Potential Disease-Modifying Therapies for Huntington\u2019s Disease: Lessons Learned and Future Opportunities","volume":"21","author":"Tabrizi","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s40259-022-00519-9","article-title":"Antisense Oligonucleotide Therapy: From Design to the Huntington Disease Clinic","volume":"36","author":"Rook","year":"2022","journal-title":"BioDrugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16976","DOI":"10.1038\/s41598-018-34883-w","article-title":"Decreased BDNF Release in Cortical Neurons of a Knock-in Mouse Model of Huntington\u2019s Disease","volume":"8","author":"Yu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.18632\/aging.202603","article-title":"Functional Analysis of Brain Derived Neurotrophic Factor (BDNF) in Huntington\u2019s Disease","volume":"13","author":"Zhou","year":"2021","journal-title":"Aging"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Speidell, A., Bin Abid, N., and Yano, H. (2023). Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington\u2019s Disease: Mechanisms and Potential Therapeutics. Biomedicines, 11.","DOI":"10.3390\/biomedicines11082275"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Plinta, K., Plewka, A., Pawlicki, K., Zmarz\u0142y, N., W\u00f3jcik-P\u0119dziwiatr, M., Rudzi\u0144ski, M., Krzak-Kubica, A., Dor\u0119gowska-Stachera, M., and Rudzi\u0144ska-Bar, M. (2021). The Utility of BDNF Detection in Assessing Severity of Huntington\u2019s Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10215181"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16872","DOI":"10.1038\/s41598-019-53410-z","article-title":"Discovery of a Potent Small Molecule Inhibiting Huntington\u2019s Disease (HD) Pathogenesis via Targeting CAG Repeats RNA and Poly Q Protein","volume":"9","author":"Khan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jarosi\u0144ska, O.D., and R\u00fcdiger, S.G.D. (2021). Molecular Strategies to Target Protein Aggregation in Huntington\u2019s Disease. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.769184"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1566-2772(03)00054-9","article-title":"Excitotoxicity in Huntington Disease","volume":"3","author":"Raymond","year":"2003","journal-title":"Clin. Neurosci. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kang, R., Wang, L., Sanders, S.S., Zuo, K., Hayden, M.R., and Raymond, L.A. (2019). Altered Regulation of Striatal Neuronal N-Methyl-D-Aspartate Receptor Trafficking by Palmitoylation in Huntington Disease Mouse Model. Front. Synaptic Neurosci., 11.","DOI":"10.3389\/fnsyn.2019.00003"},{"key":"ref_30","first-page":"499","article-title":"Glutamate and GABA Imbalance Promotes Neuronal Apoptosis in Hippocampus after Stress","volume":"20","author":"Gao","year":"2014","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1186\/s13256-023-04161-z","article-title":"Memantine Administration Prevented Chorea Movement in Huntington\u2019s Disease: A Case Report","volume":"17","author":"Saigoh","year":"2023","journal-title":"J. Med. Case Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1212\/WNL.59.5.694","article-title":"Huntington\u2019s Disease: A Randomized, Controlled Trial Using the NMDA-Antagonist Amantadine","volume":"59","author":"Morris","year":"2002","journal-title":"Neurology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/jnen\/60.2.161","article-title":"Early and Progressive Accumulation of Reactive Microglia in the Huntington Disease Brain","volume":"60","author":"Sapp","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0072-9752(07)01256-0","article-title":"Neuropathology of Huntington\u2019s Disease","volume":"Volume 89","author":"Vonsattel","year":"2008","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tizabi, Y., Getachew, B., Hauser, S.R., Tsytsarev, V., Manh\u00e3es, A.C., and Da Silva, V.D.A. (2024). Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction. Brain Sci., 14.","DOI":"10.3390\/brainsci14060558"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sanadgol, N. (2023). Editorial: Glial Cells as an Emerging Therapeutic Target in the Pathobiology of Central Nervous System Disorders: Friend or Foe?. Front. Cell. Neurosci., 17.","DOI":"10.3389\/fncel.2023.1191743"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.2174\/1570159X19666211201094608","article-title":"Neuroinflammation in Huntington\u2019s Disease: A Starring Role for Astrocyteand Microglia","volume":"20","author":"Saba","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/bs.ant.2024.02.001","article-title":"Iron Toxicity, Ferroptosis and Microbiota in Parkinson\u2019s Disease: Implications for Novel Targets","volume":"Volume 11","author":"Carvalho","year":"2024","journal-title":"Advances in Neurotoxicology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pathak, D., and Sriram, K. (2023). Neuron-Astrocyte Omnidirectional Signaling in Neurological Health and Disease. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1169320"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"De Marchi, F., Munitic, I., Vidatic, L., Papi\u0107, E., Ra\u010dki, V., Nimac, J., Jurak, I., Novotni, G., Rogelj, B., and Vuletic, V. (2023). Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders. Biomedicines, 11.","DOI":"10.20944\/preprints202309.0808.v1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in Neurodegenerative Diseases: Mechanism and Potential Therapeutic Targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1007\/s10072-020-04468-5","article-title":"The Role of Microglia in the Development of Neurodegeneration","volume":"41","author":"Saitgareeva","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Soares, \u00c9.N., Costa, A.C.D.S., Ferrolho, G.D.J., Ureshino, R.P., Getachew, B., Costa, S.L., Da Silva, V.D.A., and Tizabi, Y. (2024). Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson\u2019s Disease. Cells, 13.","DOI":"10.20944\/preprints202401.2149.v1"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liao, X., Zhu, W., Liao, X., Liu, W., Hou, Y., and Wan, J. (2024). Expression of Toll-like Receptors in the Cerebellum during Pathogenesis of Prion Disease. Front. Behav. Neurosci., 18.","DOI":"10.3389\/fnbeh.2024.1341901"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jphs.2020.07.004","article-title":"Microglia as Therapeutic Target in Central Nervous System Disorders","volume":"144","author":"Fatoba","year":"2020","journal-title":"J. Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12974-022-02496-w","article-title":"The Role of Toll-like Receptors and Neuroinflammation in Parkinson\u2019s Disease","volume":"19","author":"Heidari","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_47","first-page":"1","article-title":"Microglial Activation in Metal Neurotoxicity: Impact in Neurodegenerative Diseases","volume":"2023","author":"Ortega","year":"2023","journal-title":"BioMed Res. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.tins.2020.01.003","article-title":"Astrocytes and Microglia: In Sickness and in Health","volume":"43","author":"Vainchtein","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kotliarova, A., and Sidorova, Y.A. (2021). Glial Cell Line-Derived Neurotrophic Factor Family Ligands, Players at the Interface of Neuroinflammation and Neuroprotection: Focus Onto the Glia. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.679034"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Garland, E.F., Hartnell, I.J., and Boche, D. (2022). Microglia and Astrocyte Function and Communication: What Do We Know in Humans?. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.824888"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1152\/physrev.00042.2016","article-title":"Physiology of Astroglia","volume":"98","author":"Verkhratsky","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Stoklund Dittlau, K., and Freude, K. (2024). Astrocytes: The Stars in Neurodegeneration?. Biomolecules, 14.","DOI":"10.3390\/biom14030289"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2278222024","DOI":"10.1523\/JNEUROSCI.2278-22.2024","article-title":"Astrocytes Are the Source of TNF Mediating Homeostatic Synaptic Plasticity","volume":"44","author":"Heir","year":"2024","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.2174\/13894501113149990156","article-title":"Astrocyte Pathology in Major Depressive Disorder: Insights from Human Postmortem Brain Tissue","volume":"14","author":"Rajkowska","year":"2013","journal-title":"Curr. Drug Targets"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41582-023-00822-1","article-title":"Functional Roles of Reactive Astrocytes in Neuroinflammation and Neurodegeneration","volume":"19","author":"Patani","year":"2023","journal-title":"Nat. Rev. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.it.2020.07.007","article-title":"The Role of Astrocytes in CNS Inflammation","volume":"41","author":"Giovannoni","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.cell.2010.02.016","article-title":"Mechanisms Underlying Inflammation in Neurodegeneration","volume":"140","author":"Glass","year":"2010","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pamphlett, R., and Bishop, D.P. (2023). The Toxic Metal Hypothesis for Neurological Disorders. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1173779"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"175909142096268","DOI":"10.1177\/1759091420962681","article-title":"Iron Metabolism in Oligodendrocytes and Astrocytes, Implications for Myelination and Remyelination","volume":"12","author":"Cheli","year":"2020","journal-title":"ASN Neuro"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"147234","DOI":"10.1016\/j.brainres.2020.147234","article-title":"Astrocytes in Heavy Metal Neurotoxicity and Neurodegeneration","volume":"1752","author":"Li","year":"2021","journal-title":"Brain Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.neuro.2019.09.007","article-title":"Huntington\u2019s Disease Associated Resistance to Mn Neurotoxicity Is Neurodevelopmental Stage and Neuronal Lineage Dependent","volume":"75","author":"Joshi","year":"2019","journal-title":"Neurotoxicology"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tizabi, Y., Bennani, S., El Kouhen, N., Getachew, B., and Aschner, M. (2023). Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder. Biomolecules, 13.","DOI":"10.20944\/preprints202304.0753.v2"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Michalski, J.-P., and Kothary, R. (2015). Oligodendrocytes in a Nutshell. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00340"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/jnr.22767","article-title":"Toll-like Receptors 2 and 3 Agonists Differentially Affect Oligodendrocyte Survival, Differentiation, and Myelin Membrane Formation","volume":"90","author":"Bsibsi","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/164_2021_543","article-title":"Toll-Like Receptors in Adaptive Immunity","volume":"Volume 276","author":"Kumar","year":"2021","journal-title":"Toll-like Receptors in Health and Disease"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13287-022-02798-z","article-title":"Toll-like Receptors 2 and 4 Differentially Regulate the Self-Renewal and Differentiation of Spinal Cord Neural Precursor Cells","volume":"13","author":"Guerri","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Sun, Y., Tong, H., Yang, T., Liu, L., Li, X.-J., and Li, S. (2022). Insights into White Matter Defect in Huntington\u2019s Disease. Cells, 11.","DOI":"10.3390\/cells11213381"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Maiuolo, J., Macr\u00ec, R., Bava, I., Gliozzi, M., Musolino, V., Nucera, S., Carresi, C., Scicchitano, M., Bosco, F., and Scarano, F. (2019). Myelin Disturbances Produced by Sub-Toxic Concentration of Heavy Metals: The Role of Oligodendrocyte Dysfunction. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184554"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/nn.3815","article-title":"Modulation of Oligodendrocyte Generation during a Critical Temporal Window after NG2 Cell Division","volume":"17","author":"Hill","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Belov Kirdajova, D., Kriska, J., Tureckova, J., and Anderova, M. (2020). Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00051"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1002\/glia.22859","article-title":"NG 2-glia and Their Functions in the Central Nervous System","volume":"63","author":"Dimou","year":"2015","journal-title":"Glia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/hipo.22232","article-title":"Spatial Organization of NG2 Glial Cells and Astrocytes in Rat Hippocampal CA1 Region","volume":"24","author":"Xu","year":"2014","journal-title":"Hippocampus"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00401-016-1563-z","article-title":"NG2, a Common Denominator for Neuroinflammation, Blood\u2013Brain Barrier Alteration, and Oligodendrocyte Precursor Response in EAE, Plays a Role in Dendritic Cell Activation","volume":"132","author":"Ferrara","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zhang, S., Wang, Q., Yang, Q., Gu, H., Yin, Y., Li, Y., Hou, J., Chen, R., Sun, Q., and Sun, Y. (2019). NG2 Glia Regulate Brain Innate Immunity via TGF-\u03922\/TGFBR2 Axis. BMC Med., 17.","DOI":"10.1186\/s12916-019-1439-x"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Hu, X., Geng, P., Zhao, X., Wang, Q., Liu, C., Guo, C., Dong, W., and Jin, X. (2023). The NG2-Glia Is a Potential Target to Maintain the Integrity of Neurovascular Unit after Acute Ischemic Stroke. Neurobiol. Dis., 180.","DOI":"10.1016\/j.nbd.2023.106076"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1002\/glia.24352","article-title":"Dysfunction of NG2 Glial Cells Affects Neuronal Plasticity and Behavior","volume":"71","author":"Timmermann","year":"2023","journal-title":"Glia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6921","DOI":"10.1523\/JNEUROSCI.0238-10.2010","article-title":"Postnatal Switch from Synaptic to Extrasynaptic Transmission between Interneurons and NG2 Cells","volume":"30","author":"Maldonado","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Shoemaker, W.R., Chen, D., and Garud, N.R. (2022). Comparative Population Genetics in the Human Gut Microbiome. Genome Biol. Evol., 14.","DOI":"10.1093\/gbe\/evab116"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"155915","DOI":"10.1016\/j.scitotenv.2022.155915","article-title":"Microbiome Systems Biology Advancements for Natural Well-Being","volume":"838","author":"Chatterjee","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41576-022-00529-x","article-title":"Microbiome Epidemiology and Association Studies in Human Health","volume":"24","author":"VanEvery","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in Health and Diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/1535370217743766","article-title":"Gut Reactions: How the Blood\u2013Brain Barrier Connects the Microbiome and the Brain","volume":"243","author":"Logsdon","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Hrncir, T. (2022). Gut Microbiota Dysbiosis: Triggers, Consequences, Diagnostic and Therapeutic Options. Microorganisms, 10.","DOI":"10.3390\/microorganisms10030578"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"121882","DOI":"10.1016\/j.lfs.2023.121882","article-title":"Gut Microbiota Dysbiosis and Huntington\u2019s Disease: Exploring the Gut-Brain Axis and Novel Microbiota-Based Interventions","volume":"328","author":"Sharma","year":"2023","journal-title":"Life Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Tong, H., Yang, T., Xu, S., Li, X., Liu, L., Zhou, G., Yang, S., Yin, S., Li, X.-J., and Li, S. (2024). Huntington\u2019s Disease: Complex Pathogenesis and Therapeutic Strategies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073845"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.brainres.2018.03.015","article-title":"Neurotransmitter Modulation by the Gut Microbiota","volume":"1693","author":"Strandwitz","year":"2018","journal-title":"Brain Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Li, Y., Li, Y.-J., and Zhu, Z.-Q. (2023). To Re-Examine the Intersection of Microglial Activation and Neuroinflammation in Neurodegenerative Diseases from the Perspective of Pyroptosis. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1284214"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Buret, A.G., Motta, J.-P., Allain, T., Ferraz, J., and Wallace, J.L. (2019). Pathobiont Release from Dysbiotic Gut Microbiota Biofilms in Intestinal Inflammatory Diseases: A Role for Iron?. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-018-0495-4"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1002\/mds.28231","article-title":"Gut Microbiome Imbalance and Neuroinflammation: Impact of COVID-19 on Parkinson\u2019s Disease","volume":"35","author":"Follmer","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Silva, Y.P., Bernardi, A., and Frozza, R.L. (2020). The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00025"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3748\/wjg.v17.i12.1519","article-title":"Potential Beneficial Effects of Butyrate in Intestinal and Extraintestinal Diseases","volume":"17","author":"Canani","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Skrzypczak-Wiercioch, A., and Sa\u0142at, K. (2022). Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use. Molecules, 27.","DOI":"10.3390\/molecules27175481"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Mitrea, L., Neme\u015f, S.-A., Szabo, K., Teleky, B.-E., and Vodnar, D.-C. (2022). Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders. Front. Med., 9.","DOI":"10.3389\/fmed.2022.813204"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1136\/gutjnl-2019-318427","article-title":"Leaky Gut: Mechanisms, Measurement and Clinical Implications in Humans","volume":"68","author":"Camilleri","year":"2019","journal-title":"Gut"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"fcaa110","DOI":"10.1093\/braincomms\/fcaa110","article-title":"Gut Dysbiosis in Huntington\u2019s Disease: Associations among Gut Microbiota, Cognitive Performance and Clinical Outcomes","volume":"2","author":"Wasser","year":"2020","journal-title":"Brain Commun."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Witkowska, D., S\u0142owik, J., and Chilicka, K. (2021). Heavy Metals and Human Health: Possible Exposure Pathways and the Competition for Protein Binding Sites. Molecules, 26.","DOI":"10.3390\/molecules26196060"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Koch, W., Czop, M., I\u0142owiecka, K., Nawrocka, A., and Wi\u0105cek, D. (2022). Dietary Intake of Toxic Heavy Metals with Major Groups of Food Products\u2014Results of Analytical Determinations. Nutrients, 14.","DOI":"10.3390\/nu14081626"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Rieder, G.S., Duarte, T., Delgado, C.P., Rodighiero, A., Nogara, P.A., Orian, L., Aschner, M., Dalla Corte, C.L., and Da Rocha, J.B.T. (2024). Interplay between Diphenyl Diselenide and Copper: Impact on D. Melanogaster Survival, Behavior, and Biochemical Parameters. Comp. Biochem. Physiol. Part C Toxicol. Pharmacol., 281.","DOI":"10.1016\/j.cbpc.2024.109899"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCULATIONAHA.118.030099","article-title":"Anemia and Iron Deficiency in Heart Failure: Current Concepts and Emerging Therapies","volume":"138","author":"Anand","year":"2018","journal-title":"Circulation"},{"key":"ref_100","first-page":"946372","article-title":"The Toxic Effect of Manganese on the Acetylcholinesterase Activity in Rat Brains","volume":"2014","author":"Sadeghi","year":"2014","journal-title":"J. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-nutr-071714-034419","article-title":"Manganese Is Essential for Neuronal Health","volume":"35","author":"Horning","year":"2015","journal-title":"Annu. Rev. Nutr."},{"key":"ref_102","first-page":"31","article-title":"Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese","volume":"3","author":"Andrade","year":"2017","journal-title":"EC Pharmacol. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Peres, T.V., Schettinger, M.R.C., Chen, P., Carvalho, F., Avila, D.S., Bowman, A.B., and Aschner, M. (2016). Manganese-Induced Neurotoxicity: A Review of Its Behavioral Consequences and Neuroprotective Strategies. BMC Pharmacol. Toxicol., 17.","DOI":"10.1186\/s40360-016-0099-0"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s40572-015-0056-x","article-title":"Manganese Toxicity Upon Overexposure: A Decade in Review","volume":"2","author":"Zheng","year":"2015","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/toxsci\/kfp124","article-title":"Effects of Chronic Manganese Exposure on Glutamatergic and GABAergic Neurotransmitter Markers in the Nonhuman Primate Brain","volume":"111","author":"Burton","year":"2009","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0361-9230(94)90204-6","article-title":"Manganese (Mn) Transport across the Rat Blood-Brain Barrier: Saturable and Transferrin-Dependent Transport Mechanisms","volume":"33","author":"Aschner","year":"1994","journal-title":"Brain Res. Bull."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: Molecular Mechanisms and Health Implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Ji, Y., Zheng, K., Li, S., Ren, C., Shen, Y., Tian, L., Zhu, H., Zhou, Z., and Jiang, Y. (2022). Insight into the Potential Role of Ferroptosis in Neurodegenerative Diseases. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.1005182"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Lee, J.-Y., Kim, W.K., Bae, K.-H., Lee, S.C., and Lee, E.-W. (2021). Lipid Metabolism and Ferroptosis. Biology, 10.","DOI":"10.3390\/biology10030184"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Tian, H.-Y., Huang, B.-Y., Nie, H.-F., Chen, X.-Y., Zhou, Y., Yang, T., Cheng, S.-W., Mei, Z.-G., and Ge, J.-W. (2023). The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases. Brain Sci., 13.","DOI":"10.20944\/preprints202308.0327.v1"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Feng, S., Tang, D., Wang, Y., Li, X., Bao, H., Tang, C., Dong, X., Li, X., Yang, Q., and Yan, Y. (2023). The Mechanism of Ferroptosis and Its Related Diseases. Mol. Biomed., 4.","DOI":"10.1186\/s43556-023-00142-2"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: Past, Present and Future","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, Biology and Role in Disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Reichert, C.O., de Freitas, F.A., Sampaio-Silva, J., Rokita-Rosa, L., Barros, P.d.L., Levy, D., and Bydlowski, S.P. (2020). Ferroptosis Mechanisms Involved in Neurodegenerative Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228765"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Johnson, E.B., Parker, C.S., Scahill, R.I., Gregory, S., Papoutsi, M., Zeun, P., Osborne-Crowley, K., Lowe, J., Nair, A., and Estevez-Fraga, C. (2021). Altered Iron and Myelin in Premanifest Huntington\u2019s Disease More than 20 Years before Clinical Onset: Evidence from the Cross-Sectional HD Young Adult Study. EBioMedicine, 65.","DOI":"10.1016\/j.ebiom.2021.103266"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/s41380-023-02399-z","article-title":"Iron Imbalance in Neurodegeneration","volume":"29","author":"Levi","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Mancardi, D., Mezzanotte, M., Arrigo, E., Barinotti, A., and Roetto, A. (2021). Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver. Antioxidants, 10.","DOI":"10.3390\/antiox10121864"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"9187195","DOI":"10.1155\/2020\/9187195","article-title":"Blood Oxidative Stress Marker Aberrations in Patients with Huntington\u2019s Disease: A Meta-Analysis Study","volume":"2020","author":"Tang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Paul, B.D., and Snyder, S.H. (2019). Impaired Redox Signaling in Huntington\u2019s Disease: Therapeutic Implications. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00068"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Chen, J., Marks, E., Lai, B., Zhang, Z., Duce, J.A., Lam, L.Q., Volitakis, I., Bush, A.I., Hersch, S., and Fox, J.H. (2013). Iron Accumulates in Huntington\u2019s Disease Neurons: Protection by Deferoxamine. PLoS ONE, 8.","DOI":"10.1371\/annotation\/67f555f5-35b7-4468-8bab-26d518942803"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1038\/s41467-023-38444-2","article-title":"Microbiota-Assisted Iron Uptake Promotes Immune Tolerance in the Intestine","volume":"14","author":"Zhu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Correnti, M., Gammella, E., Cairo, G., and Recalcati, S. (2024). Iron Absorption: Molecular and Pathophysiological Aspects. Metabolites, 14.","DOI":"10.3390\/metabo14040228"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Patan\u00e8, G.T., Putaggio, S., Tellone, E., Barreca, D., Ficarra, S., Maffei, C., Calderaro, A., and Lagan\u00e0, G. (2023). Ferroptosis: Emerging Role in Diseases and Potential Implication of Bioactive Compounds. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417279"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s41392-023-01606-1","article-title":"Targeting Ferroptosis Opens New Avenues for the Development of Novel Therapeutics","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhang, Y., Ji, M., Wu, C., Zhang, Y., and Ji, S. (2024). Targeting Ferroptosis in Neuroimmune and Neurodegenerative Disorders for the Development of Novel Therapeutics. Biomed. Pharmacother., 176.","DOI":"10.1016\/j.biopha.2024.116777"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.mam.2005.07.003","article-title":"Nutritional Aspects of Manganese Homeostasis","volume":"26","author":"Aschner","year":"2005","journal-title":"Mol. Aspects Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/7580707","article-title":"The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions","volume":"2018","author":"Li","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12640-023-00682-z","article-title":"Butyrate Protects and Synergizes with Nicotine against Iron- and Manganese-Induced Toxicities in Cell Culture","volume":"42","author":"Tizabi","year":"2024","journal-title":"Neurotox. Res."},{"key":"ref_130","unstructured":"Evans, G.R., and Masullo, L.N. (2024). Manganese Toxicity. StatPearls, StatPearls Publishing."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"123732","DOI":"10.1016\/j.envpol.2024.123732","article-title":"The Effects of Heavy Metal Exposure on Brain and Gut Microbiota: A Systematic Review of Animal Studies","volume":"348","author":"Porru","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"100170","DOI":"10.1016\/j.crtox.2024.100170","article-title":"Manganese in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: The State of the Art","volume":"6","author":"Aschner","year":"2024","journal-title":"Curr. Res. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-3-319-60189-2_6","article-title":"Manganese and the Insulin-IGF Signaling Network in Huntington\u2019s Disease and Other Neurodegenerative Disorders","volume":"Volume 18","author":"Aschner","year":"2017","journal-title":"Neurotoxicity of Metals"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.neuro.2023.06.005","article-title":"Toxicity of Copper and Zinc Alone and in Combination in Caenorhabditis Elegans Model of Huntington\u2019s Disease and Protective Effects of Rutin","volume":"97","author":"Cordeiro","year":"2023","journal-title":"Neurotoxicology"},{"key":"ref_135","unstructured":"Royer, A., and Sharman, T. (2024). Copper Toxicity. StatPearls, StatPearls Publishing."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Opazo, C.M., Lotan, A., Xiao, Z., Zhang, B., Greenough, M.A., Lim, C.M., Trytell, H., Ram\u00edrez, A., Ukuwela, A.A., and Mawal, C.H. (2021). Nutrient Copper Signaling Promotes Protein Turnover by Allosteric Activation of Ubiquitin E2D Conjugases. bioRxiv.","DOI":"10.1101\/2021.02.15.431211"},{"key":"ref_137","unstructured":"Immergluck, J., and Anilkumar, A.C. (2024). Wilson Disease. StatPearls, StatPearls Publishing."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"14995","DOI":"10.1073\/pnas.1308535110","article-title":"Huntington Disease Arises from a Combinatory Toxicity of Polyglutamine and Copper Binding","volume":"110","author":"Xiao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"10373","DOI":"10.1038\/s41598-022-14169-y","article-title":"Alterations in Metal Homeostasis Occur Prior to Canonical Markers in Huntington Disease","volume":"12","author":"Pfalzer","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1001\/archneurol.2011.2945","article-title":"Alterations in Brain Transition Metals in Huntington Disease: An Evolving and Intricate Story","volume":"69","author":"Rosas","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"366","DOI":"10.12688\/f1000research.7431.1","article-title":"Metals and Neurodegeneration","volume":"5","author":"Chen","year":"2016","journal-title":"F1000Research"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuro.2018.10.012","article-title":"Heterozygous Huntingtin Promotes Cadmium Neurotoxicity and Neurodegeneration in Striatal Cells via Altered Metal Transport and Protein Kinase C Delta Dependent Oxidative Stress and Apoptosis Signaling Mechanisms","volume":"70","author":"Kwakye","year":"2019","journal-title":"Neurotoxicology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.toxrep.2023.04.010","article-title":"Disease-Associated Metabolic Pathways Affected by Heavy Metals and Metalloid","volume":"10","author":"Haidar","year":"2023","journal-title":"Toxicol. Rep."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Suganya, K., and Koo, B.-S. (2020). Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics\/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207551"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/bs.irn.2022.06.005","article-title":"The Microbiota-Gut-Brain Axis in Huntington\u2019s Disease","volume":"Volume 167","author":"Love","year":"2022","journal-title":"International Review of Neurobiology"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Wronka, D., Karlik, A., Misiorek, J.O., and Przybyl, L. (2023). What the Gut Tells the Brain\u2014Is There a Link between Microbiota and Huntington\u2019s Disease?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054477"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Ekwudo, M.N., Gubert, C., and Hannan, A.J. (2024). The Microbiota\u2013Gut\u2013Brain Axis in Huntington\u2019s Disease: Pathogenic Mechanisms and Therapeutic Targets. FEBS J., online ahead of print.","DOI":"10.1111\/febs.17102"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1007\/s12640-020-00238-5","article-title":"Butyrate Protects Against Salsolinol-Induced Toxicity in SH-SY5Y Cells: Implication for Parkinson\u2019s Disease","volume":"38","author":"Getachew","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1007\/s12640-021-00418-x","article-title":"Sodium Butyrate Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line","volume":"39","author":"Getachew","year":"2021","journal-title":"Neurotox. Res."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Batista, C.R.A., Gomes, G.F., Candelario-Jalil, E., Fiebich, B.L., and de Oliveira, A.C.P. (2019). Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092293"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Breit, S., Kupferberg, A., Rogler, G., and Hasler, G. (2018). Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front. Psychiatry, 9.","DOI":"10.3389\/fpsyt.2018.00044"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"103687","DOI":"10.1016\/j.isci.2021.103687","article-title":"Gene-Environment-Gut Interactions in Huntington\u2019s Disease Mice Are Associated with Environmental Modulation of the Gut Microbiome","volume":"25","author":"Gubert","year":"2022","journal-title":"iScience"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.2147\/IDR.S254403","article-title":"The Impact of Gut Microbiota Disorders on the Blood\u2013Brain Barrier","volume":"13","author":"Tang","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"5332","DOI":"10.1038\/s41598-023-32630-4","article-title":"Quantifying Mutant Huntingtin Protein in Human Cerebrospinal Fluid to Support the Development of Huntingtin-Lowering Therapies","volume":"13","author":"Vauleon","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e22301","DOI":"10.1002\/syn.22301","article-title":"New Insights into Sodium Phenylbutyrate as a Pharmacotherapeutic Option for Neurological Disorders","volume":"78","author":"Juarez","year":"2024","journal-title":"Synapse"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40035-024-00404-1","article-title":"Therapeutics for Neurodegenerative Diseases by Targeting the Gut Microbiome: From Bench to Bedside","volume":"13","author":"Ma","year":"2024","journal-title":"Transl. 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