<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">actabiomedica</journal-id><journal-title-group><journal-title xml:lang="ru">Acta Biomedica Scientifica</journal-title><trans-title-group xml:lang="en"><trans-title>Acta Biomedica Scientifica</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2541-9420</issn><issn pub-type="epub">2587-9596</issn><publisher><publisher-name>Scientific Centre for Family Health and Human Reproduction Problems</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29413/ABS.2025-10.1.17</article-id><article-id custom-type="elpub" pub-id-type="custom">actabiomedica-5227</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>НЕВРОЛОГИЯ И НЕЙРОХИРУРГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>NEUROLOGY AND NEUROSURGERY</subject></subj-group></article-categories><title-group><article-title>Причины чрезмерного накопления железа в структурах чёрного вещества головного мозга при болезни Паркинсона</article-title><trans-title-group xml:lang="en"><trans-title>Causes of accumulation of excess iron in the structures of the substantia nigra of the brain in Parkinson’s disease</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1580-0380</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сальков</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Salkov</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сальков Владимир Николаевич – доктор медицинских наук, старший научный сотрудник лаборатории нейроморфологии Института мозга, </p><p>125367, г. Москва, Волоколамское шоссе, 80</p></bio><bio xml:lang="en"><p>Vladimir N. Salkov – Dr. Sc. (Med.), Senior Research Officer at the Laboratory of  Neuromorphology, Brain Institute, </p><p>Volokolamskoye Highway 80, Moscow 125367</p></bio><email xlink:type="simple">vla-salkov@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научный центр неврологии»</institution></aff><aff xml:lang="en"><institution>Research Center of Neurology</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>20</day><month>03</month><year>2025</year></pub-date><volume>10</volume><issue>1</issue><fpage>161</fpage><lpage>168</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Сальков В.Н., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Сальков В.Н.</copyright-holder><copyright-holder xml:lang="en">Salkov V.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.actabiomedica.ru/jour/article/view/5227">https://www.actabiomedica.ru/jour/article/view/5227</self-uri><abstract><p>Представлен критический анализ литературы о факторах, способствующих чрезмерному накоплению железа в структурах чёрного вещества головного мозга при болезни Паркинсона. Этот морфологический признак наряду с такими признаками, как накопление в дофаминовых нейронах аномальной формы пресинаптического белка альфа-синуклеина, их  быстрая гибель и глиоз в чёрном веществе головного мозга, является одним из важнейших в патоморфологической картине заболевания.</p><p>Показано, что избыток железа в чёрном веществе может быть обусловлен влиянием таких факторов, как  воздействие токсичных металлов (алюминий, ртуть и свинец) на головной мозг, нарушение проницаемости гематоэнцефалического барьера, изменение экспрессии металлосодержащих белков и генетические мутации. Вместе с тем роль таких факторов, как употребление большого количества железа с пищевыми продуктами и  биологическими добавками к  пище и  митохондриальная дисфункция, в формировании данного морфологического признака болезни Паркинсона остаётся до конца не изученной.</p><p>Продолжение изучения причин накопления избытка железа в  структурах среднего мозга при болезни Паркинсона и тех последствий, которые могут быть обусловлены чрезмерным накоплением железа в  этих структурах, остаётся актуальным для современной неврологии.</p><p>Поиск литературы проводился в базах данных PubMed и eLIBRARY.</p></abstract><trans-abstract xml:lang="en"><p>A critical analysis of the literature on the factors contributing to the excessive accumulation of iron in the structures of the substantia nigra of the brain in Parkinson’s disease is presented. This morphological feature, along with such signs as the accumulation of an abnormal form of presynaptic protein alpha-synuclein in dopamine neurons, their rapid death and gliosis in the substantia nigra of the brain, is one of the most important in the pathomorphological picture of the disease.</p><p>It is shown that the excess of iron in the substantia nigra may be due to the influence of such factors as the effects of toxic metals (aluminum, mercury and lead) on the brain, impaired permeability of the blood-brain barrier, changes in the expression of metal-containing proteins and genetic mutations. At the same time, the role of factors such as the consumption of large amounts of iron with food and dietary supplements, and mitochondrial dysfunction in the formation of this morphological sign of Parkinson’s disease remains not fully understood.</p><p>Continuation of the study of the causes of accumulation of excess iron in the structures of the midbrain in Parkinson's disease and those consequences that may be caused by excessive accumulation of iron in these structures remain relevant for modern neurology.</p><p>The literature search was conducted in the databases PubMed and eLibrary.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>болезнь Паркинсона</kwd><kwd>чёрное вещество</kwd><kwd>накопление железа</kwd><kwd>тяжёлые металлы</kwd><kwd>гематоэнцефалический барьер</kwd><kwd>железосодержащие белки</kwd><kwd>генетические мутации</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Parkinson’s disease</kwd><kwd>substantia nigra</kwd><kwd>iron accumulation</kwd><kwd>heavy metals</kwd><kwd>blood-brain barrier</kwd><kwd>iron-containing proteins</kwd><kwd>genetic mutations</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Hayes MT. Parkinson’s disease and parkinsonism. Am J Med. 2019; 132(7): 802-807. doi: 10.1016/j.amjmed.2019.03.001</mixed-citation><mixed-citation xml:lang="en">Hayes MT. Parkinson’s disease and parkinsonism. Am J Med. 2019; 132(7): 802-807. doi: 10.1016/j.amjmed.2019.03.001</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Sveinbjornsdottir S. The clinical symptoms of Parkinson’s disease. J Neurochem. 2016; 139(1): 318-324. doi: 10.1111/jnc.13691</mixed-citation><mixed-citation xml:lang="en">Sveinbjornsdottir S. The clinical symptoms of Parkinson’s disease. J Neurochem. 2016; 139(1): 318-324. doi: 10.1111/jnc.13691</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Skou LD, Johansen SK, Okarmus J, Meyer M. Pathogenesis of DJ-1/PARK7-mediated Parkinson’s disease. Cells. 2024; 13(4): 296. doi: 10.3390/cells13040296</mixed-citation><mixed-citation xml:lang="en">Skou LD, Johansen SK, Okarmus J, Meyer M. Pathogenesis of DJ-1/PARK7-mediated Parkinson’s disease. Cells. 2024; 13(4): 296. doi: 10.3390/cells13040296</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Thomas GEC, Zarkali A, Ryten M, Shmueli K, Gil-Martinez AL, Leyland LA, et al. Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease. Brain. 2021; 144(6): 1787-1798. doi: 10.1093/brain/awab084</mixed-citation><mixed-citation xml:lang="en">Thomas GEC, Zarkali A, Ryten M, Shmueli K, Gil-Martinez AL, Leyland LA, et al. Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease. Brain. 2021; 144(6): 1787-1798. doi: 10.1093/brain/awab084</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Hare DJ, Double KL. Iron and dopamine: A toxic couple. Brain. 2016; 139: 1026-1035. doi: 10.1093/brain/aww022</mixed-citation><mixed-citation xml:lang="en">Hare DJ, Double KL. Iron and dopamine: A toxic couple. Brain. 2016; 139: 1026-1035. doi: 10.1093/brain/aww022</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Zeng W, Cai J, Zhang L, Peng Q. Iron deposition in Parkinson’s disease: A mini-review. Cell Mol Neurobiol. 2024; 44(1): 26. doi: 10.1007/s10571-024-01459-4</mixed-citation><mixed-citation xml:lang="en">Zeng W, Cai J, Zhang L, Peng Q. Iron deposition in Parkinson’s disease: A mini-review. Cell Mol Neurobiol. 2024; 44(1): 26. doi: 10.1007/s10571-024-01459-4</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Knörle R. Neuromelanin in Parkinson’s disease: From Fenton reaction to calcium signaling. Neurotox Res. 2018; 33(2): 515-522. doi: 10.1007/s12640-017-9804-z</mixed-citation><mixed-citation xml:lang="en">Knörle R. Neuromelanin in Parkinson’s disease: From Fenton reaction to calcium signaling. Neurotox Res. 2018; 33(2): 515-522. doi: 10.1007/s12640-017-9804-z</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">David S, Jhelum P, Ryan F, Jeong SY, Kroner A. Dysregulation of iron homeostasis in the central nervous system and the role of ferroptosis in neurodegenerative disorders. Antioxid Redox Signal. 2022; 37: 150-170. doi: 10.1089/ars.2021.0218</mixed-citation><mixed-citation xml:lang="en">David S, Jhelum P, Ryan F, Jeong SY, Kroner A. Dysregulation of iron homeostasis in the central nervous system and the role of  ferroptosis in  neurodegenerative disorders. Antioxid Redox Signal. 2022; 37: 150-170. doi: 10.1089/ars.2021.0218</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Roe K. An alternative explanation for Alzheimer’s disease and Parkinson’s disease initiation from specific antibiotics, gut microbiota dysbiosis and neurotoxins. Neurochem Res. 2022; 47(3): 517-530. doi: 10.1007/s11064-021-03467-y</mixed-citation><mixed-citation xml:lang="en">Roe K. An alternative explanation for Alzheimer’s disease and  Parkinson’s disease initiation from  specific antibiotics, gut microbiota dysbiosis and neurotoxins. Neurochem Res. 2022; 47(3): 517-530. doi: 10.1007/s11064-021-03467-y</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, et al. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol. 2005; 57(2): 176-179. doi: 10.1002/ana.20369</mixed-citation><mixed-citation xml:lang="en">Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, et al. Blood-brain barrier dysfunction in parkinsonian midbrain in  vivo. Ann Neurol. 2005; 57(2): 176-179. doi: 10.1002/ana.20369</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014; 13(10): 1045-1060. doi: 10.1016/s1474-4422(14)70117-6</mixed-citation><mixed-citation xml:lang="en">Ward  RJ, Zucca  FA, Duyn  JH, Crichton  RR, Zecca  L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014; 13(10): 1045-1060. doi: 10.1016/s1474-4422(14)70117-6</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Guerreiro RJ, Bras JM, Santana I, Januario C, Santiago B, Morgadinho AS, et al. Association of HFE common mutations with Parkinson’s disease, Alzheimer’s disease and mild cognitive impairment in a Portuguese cohort. BMC Neurol. 2006; 6: 24. doi: 10.1186/1471-2377-6-24</mixed-citation><mixed-citation xml:lang="en">Guerreiro RJ, Bras JM, Santana I, Januario C, Santiago B, Morgadinho  AS, et  al. Association of  HFE common mutations with  Parkinson’s disease, Alzheimer’s disease and  mild cognitive impairment in a Portuguese cohort. BMC Neurol. 2006; 6: 24. doi: 10.1186/1471-2377-6-24</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Li Y, Jiao Q, Xu H, Du X, Shi L, Jia F, et al. Biometal dyshomeostasis and toxic metal accumulations in the development of Alzheimer’s disease. Front Mol Neurosci. 2017; 10: 339. doi: 10.3389/fnmol.2017.00339</mixed-citation><mixed-citation xml:lang="en">Li Y, Jiao Q, Xu H, Du X, Shi L, Jia F, et al. Biometal dyshomeostasis and toxic metal accumulations in the development of Alzheimer’s disease. Front Mol Neurosci. 2017; 10: 339. doi: 10.3389/fnmol.2017.00339</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Foley PB, Hare DJ, Double KL. A brief history of brain iron accumulation in Parkinson disease and related disorders. J Neural Transm (Vienna). 2022; 129(5-6): 505-520. doi: 10.1007/s00702-022-02505-5</mixed-citation><mixed-citation xml:lang="en">Foley PB, Hare DJ, Double KL. A brief history of brain iron accumulation in Parkinson disease and related disorders. J Neural Transm (Vienna). 2022; 129(5-6): 505-520. doi:  10.1007/s00702-022-02505-5</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Zecca L, Pietra R, Goj C, Mecacci C, Radice D, Sabbioni E. Iron and other metals in neuromelanin, substantia nigra, and putamen of human brain. J Neurochem. 1994; 62(3): 1097-1101. doi: 10.1046/j.1471-4159.1994.62031097.x</mixed-citation><mixed-citation xml:lang="en">Zecca L, Pietra R, Goj C, Mecacci C, Radice D, Sabbioni E. Iron and other metals in neuromelanin, substantia nigra, and putamen of  human brain. J  Neurochem. 1994; 62(3): 1097-1101. doi: 10.1046/j.1471-4159.1994.62031097.x</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Biesemeier A, Eibl O, Eswara S, Audinot JN, Wirtz T, Pezzoli G, et al. Elemental mapping of neuromelanin organelles of human substantia nigra: Correlative ultrastructural and chemical analysis by analytical transmission electron microscopy and nanosecondary ion mass spectrometry. J Neurochem. 2016; 138(2): 339-353. doi: 10.1111/jnc.13648</mixed-citation><mixed-citation xml:lang="en">Biesemeier A, Eibl O, Eswara S, Audinot JN, Wirtz T, Pezzoli G, et al. Elemental mapping of neuromelanin organelles of human substantia nigra: Correlative ultrastructural and  chemical analysis by analytical transmission electron microscopy and nanosecondary ion mass spectrometry. J  Neurochem. 2016; 138(2): 339-353. doi: 10.1111/jnc.13648</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Igbokwe IO, Igwenagu E, Igbokwe NA. Aluminium toxicosis: A review of toxic actions and effects. Interdiscip Toxicol. 2019; 12(2): 45-70. doi: 10.2478/intox-2019-0007</mixed-citation><mixed-citation xml:lang="en">Igbokwe IO, Igwenagu E, Igbokwe NA. Aluminium toxicosis: A review of toxic actions and effects. Interdiscip Toxicol. 2019; 12(2): 45-70. doi: 10.2478/intox-2019-0007</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Pamphlett R, Bishop DP. The toxic metal hypothesis for neurological disorders. Front Neurol. 2023; 14: 1173779. doi: 10.3389/fneur.2023.1173779</mixed-citation><mixed-citation xml:lang="en">Pamphlett  R, Bishop  DP. The  toxic metal hypothesis for neurological disorders. Front Neurol. 2023; 14: 1173779. doi: 10.3389/fneur.2023.1173779</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Schäffer E, Piel J. Das Exposom im Fokus prlventiver Maznahmen für die Alzheimer- und Parkinson-Erkrankung [The exposome in the context of preventive measures for Alzheimer’s and Parkinson’s diseases]. Nervenarzt. 2023; 94(10): 892-903. (In German). doi: 10.1007/s00115-023-01538-9</mixed-citation><mixed-citation xml:lang="en">Schäffer  E, Piel  J. Das  Exposom im  Fokus prlventiver Maznahmen für die Alzheimer- und Parkinson-Erkrankung [The exposome in  the  context of  preventive measures for  Alzheimer’s and  Parkinson’s diseases]. Nervenarzt. 2023; 94(10): 892-903. (In German). doi: 10.1007/s00115-023-01538-9</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Gunnarsson LG, Bodin L. Occupational exposures and neurodegenerative diseases – A systematic literature review and meta-analyses. Int J Environ Res Public Health. 2019; 16(3): 337. doi: 10.3390/ijerph16030337</mixed-citation><mixed-citation xml:lang="en">Gunnarsson  LG, Bodin  L. Occupational exposures and neurodegenerative diseases – A systematic literature review and meta-analyses. Int J Environ Res Public Health. 2019; 16(3): 337. doi: 10.3390/ijerph16030337</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Garza-Lombу C, Posadas Y, Quintanar L, Gonsebatt ME, Franco R. Neurotoxicity linked to dysfunctional metal ion homeostasis and xenobiotic metal exposure: Redox signaling and oxidative stress. Antioxid Redox Signal. 2018; 28(18): 1669-1703. doi: 10.1089/ars.2017.7272</mixed-citation><mixed-citation xml:lang="en">Garza-Lombу C, Posadas Y, Quintanar L, Gonsebatt ME, Franco  R. Neurotoxicity linked to  dysfunctional metal ion homeostasis and  xenobiotic metal exposure: Redox signaling and oxidative stress. Antioxid Redox Signal. 2018; 28(18): 1669-1703. doi: 10.1089/ars.2017.7272</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Mezzaroba L, Alfieri DF, Colado Simão AN, Vissoci Reiche EM. The role of zinc, copper, manganese and iron in neurodegenerative diseases. Neurotoxicology. 2019; 74: 230-241. doi: 10.1016/j.neuro.2019.07.007</mixed-citation><mixed-citation xml:lang="en">Mezzaroba  L, Alfieri  DF, Colado  Simão  AN, Vissoci  Reiche  EM. The  role of  zinc, copper, manganese and  iron in  neurodegenerative diseases. Neurotoxicology. 2019; 74: 230-241. doi: 10.1016/j.neuro.2019.07.007</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Schofield K. The metal neurotoxins: An important role in current human neural epidemics? Int J Environ Res Public Health. 2017; 14(12): 1511. doi: 10.3390/ijerph14121511</mixed-citation><mixed-citation xml:lang="en">Schofield  K. The  metal neurotoxins: An  important role in current human neural epidemics? Int J Environ Res Public Health. 2017; 14(12): 1511. doi: 10.3390/ijerph14121511</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Baj J, Flieger W, Barbachowska A, Kowalska B, Flieger M, Forma A, et al. Consequences of disturbing manganese homeostasis. Int J Mol Sci. 2023; 24(19): 14959. doi: 10.3390/ijms241914959</mixed-citation><mixed-citation xml:lang="en">Baj J, Flieger W, Barbachowska A, Kowalska B, Flieger M, Forma A, et al. Consequences of disturbing manganese homeostasis. Int J Mol Sci. 2023; 24(19): 14959. doi: 10.3390/ijms241914959</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Gуrska A, Markiewicz-Gospodarek A, Markiewicz R, Chilimoniuk Z, Borowski B, Trubalski M, et al. Distribution of iron, copper, zinc and cadmium in glia, their influence on glial cells and relationship with neurodegenerative diseases. Brain Sci. 2023; 13(6): 911. doi: 10.3390/brainsci13060911</mixed-citation><mixed-citation xml:lang="en">Gуrska  A, Markiewicz-Gospodarek  A, Markiewicz  R, Chilimoniuk Z, Borowski B, Trubalski M, et al. Distribution of iron, copper, zinc and  cadmium in  glia, their influence on  glial cells and relationship with neurodegenerative diseases. Brain Sci. 2023; 13(6): 911. doi: 10.3390/brainsci13060911</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Bakulski KM, Seo YA, Hickman RC, Brandt D, Vadari HS, Hu H, et al. Heavy metals exposure and Alzheimer’s disease and related dementias. J Alzheimers Dis. 2020; 76(4): 1215-1242. doi: 10.3233/JAD-200282</mixed-citation><mixed-citation xml:lang="en">Bakulski KM, Seo YA, Hickman RC, Brandt D, Vadari HS, Hu  H, et  al. Heavy metals exposure and  Alzheimer’s disease and related dementias. J Alzheimers Dis. 2020; 76(4): 1215-1242. doi: 10.3233/JAD-200282</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Hémadi M, Miquel G, Kahn PH, El Hage Chahine JM. Aluminum exchange between citrate and human serum transferrin and interaction with transferrin receptor 1. Biochemistry. 2003; 42(10): 3120-3130. doi: 10.1021/bi020627p</mixed-citation><mixed-citation xml:lang="en">Hémadi M, Miquel G, Kahn PH, El Hage Chahine JM. Aluminum exchange between citrate and human serum transferrin and  interaction with  transferrin receptor  1. Biochemistry. 2003; 42(10): 3120-3130. doi: 10.1021/bi020627p</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Guo M, Ji X, Liu J. Hypoxia and alpha-synuclein: Inextricable link underlying the pathologic progression of Parkinson’s disease. Front Aging Neurosci. 2022; 14: 919343. doi: 10.3389/fnagi.2022.919343</mixed-citation><mixed-citation xml:lang="en">Guo M, Ji X, Liu J. Hypoxia and alpha-synuclein: Inextricable link underlying the  pathologic progression of  Parkinson’s disease. Front Aging Neurosci. 2022; 14: 919343. doi: 10.3389/fnagi.2022.919343</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Carboni E, Lingor P. Insights on the interaction of alphasynuclein and metals in the pathophysiology of Parkinson’s disease. Metallomics. 2015; 7: 395-404. doi: 10.1039/c4mt00339j</mixed-citation><mixed-citation xml:lang="en">Carboni E, Lingor P. Insights on the interaction of alphasynuclein and metals in the pathophysiology of Parkinson’s disease. Metallomics. 2015; 7: 395-404. doi: 10.1039/c4mt00339j</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Bartels AL, Willemsen AT, Kortekaas R, de Jong BM, de Vries R, de Klerk O, et al. Decreased blood-brain barrier Pglycoprotein function in the progression of Parkinson’s disease, PSP and MSA. J Neural Transm (Vienna). 2008; 115(7): 1001-1009. doi: 10.1007/s00702-008-0030-y</mixed-citation><mixed-citation xml:lang="en">Bartels  AL, Willemsen  AT, Kortekaas  R, de  Jong  BM, de Vries  R, de  Klerk  O, et  al. Decreased blood-brain barrier Pglycoprotein function in the progression of Parkinson’s disease, PSP and MSA. J Neural Transm (Vienna). 2008; 115(7): 1001-1009. doi: 10.1007/s00702-008-0030-y</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Benarroch EE. The locus ceruleus norepinephrine system: Functional organization and potential clinical significance. Neurology. 2009; 73(20): 1699-1704. doi: 10.1212/WNL.0b013e3181c2937c</mixed-citation><mixed-citation xml:lang="en">Benarroch EE. The locus ceruleus norepinephrine system: Functional organization and potential clinical significance. Neurology. 2009; 73(20): 1699-1704. doi: 10.1212/WNL.0b013e3181c2937c</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Yuan Y, Sun J, Dong Q, Cui M. Blood-brain barrier endothelial cells in neurodegenerative diseases: signals from the “barrier”. Front Neurosci. 2023; 17: 1047778. doi: 10.3389/fnins.2023.1047778</mixed-citation><mixed-citation xml:lang="en">Yuan  Y, Sun  J, Dong  Q, Cui  M. Blood-brain barrier endothelial cells in  neurodegenerative diseases: signals from the “barrier”. Front Neurosci. 2023; 17: 1047778. doi: 10.3389/fnins.2023.1047778</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Baksi S, Tripathi AK, Singh N. Alpha-synuclein modulates retinal iron homeostasis by facilitating the uptake of transferrinbound iron: Implications for visual manifestations of Parkinson’s disease. Free Radic Biol Med. 2016; 97: 292-306. doi: 10.1016/j.freeradbiomed.2016.06.025</mixed-citation><mixed-citation xml:lang="en">Baksi S, Tripathi AK, Singh N. Alpha-synuclein modulates retinal iron homeostasis by facilitating the uptake of transferrinbound iron: Implications for visual manifestations of Parkinson’s disease. Free Radic Biol Med. 2016; 97: 292-306. doi:  10.1016/j.freeradbiomed.2016.06.025</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Trist BG, Hare DJ, Double KL. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease. Aging Cell. 2019; 18(6). 00:e13031. doi: 10.1111/acel.13031</mixed-citation><mixed-citation xml:lang="en">Trist BG, Hare DJ, Double KL. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease. Aging Cell. 2019; 18(6). 00:e13031. doi: 10.1111/acel.13031</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Wang J, Bi M, Liu H, Song N, Xie J. The protective effect of lactoferrin on ventral mesencephalon neurons against MPP+ is not connected with its iron binding ability. Sci Rep. 2015; 5: 10729. doi: 10.1038/srep10729</mixed-citation><mixed-citation xml:lang="en">Wang J, Bi M, Liu H, Song N, Xie J. The protective effect of lactoferrin on ventral mesencephalon neurons against MPP+ is not connected with its iron binding ability. Sci Rep. 2015; 5: 10729. doi: 10.1038/srep10729</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Koziorowski D, Friedman A, Arosio P, Santambrogio P, Dziewulska D. ELISA reveals a difference in the structure of substantia nigra ferritin in Parkinson’s disease and incidental Lewy body compared to control. Parkinsonism Relat Disord. 2007; 13(4): 214–218. doi: 10.1016/j.parkreldis.2006.10.002</mixed-citation><mixed-citation xml:lang="en">Koziorowski  D, Friedman  A, Arosio  P, Santambrogio  P, Dziewulska D. ELISA reveals a difference in the structure of substantia nigra ferritin in  Parkinson’s disease and  incidental Lewy body compared to control. Parkinsonism Relat Disord. 2007; 13(4): 214–218. doi: 10.1016/j.parkreldis.2006.10.002</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">James SA, Roberts BR, Hare DJ, de Jonge MD, Birchall IE, Jenkins NL, et al. Direct in vivo imaging of ferrous iron dyshomeostasis in ageing Caenorhabditis elegans. Chem Sci. 2015; 6(5): 2952-2962. doi: 10.1039/c5sc00233h</mixed-citation><mixed-citation xml:lang="en">James SA, Roberts BR, Hare DJ, de Jonge MD, Birchall IE, Jenkins  NL, et  al. Direct in  vivo imaging of  ferrous iron dyshomeostasis in ageing Caenorhabditis elegans. Chem Sci. 2015; 6(5): 2952-2962. doi: 10.1039/c5sc00233h</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Salazar J, Mena N, Hunot S, Prigent A, Alvarez-Fischer D, Arredondo M, et al. Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson’s disease. Proc Natl Acad Sci U S A. 2008; 105(47): 18578-18583. doi: 10.1073/pnas.0804373105</mixed-citation><mixed-citation xml:lang="en">Salazar J, Mena N, Hunot S, Prigent A, Alvarez-Fischer D, Arredondo M, et al. Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson’s disease. Proc Natl Acad Sci U S A. 2008; 105(47): 18578-18583. doi: 10.1073/pnas.0804373105</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Hirsch EC. Iron transport in Parkinson’s disease. Parkinsonism Relat Disord. 2009; 15(3): 209-211. doi: 10.1016/S1353-8020(09)70816-8</mixed-citation><mixed-citation xml:lang="en">Hirsch EC. Iron transport in Parkinson’s disease. Parkinsonism Relat Disord. 2009; 15(3): 209-211. doi: 10.1016/S1353-8020(09)70816-8</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Hare D, Ayton S, Bush A, Lei P. A delicate balance: Iron metabolism and diseases of the brain. Front Aging Neurosci. 2013; 5: 34. doi: 10.3389/fnagi.2013.00034</mixed-citation><mixed-citation xml:lang="en">Hare D, Ayton S, Bush A, Lei P. A delicate balance: Iron metabolism and diseases of the brain. Front Aging Neurosci. 2013; 5: 34. doi: 10.3389/fnagi.2013.00034</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Sian-Hulsmann J, Riederer P. The role of alpha-synuclein as ferrireductase in neurodegeneration associated with Parkinson’s disease. J Neural Transm (Vienna). 2020; 127(5): 749-754. doi: 10.1007/s00702-020-02192-0</mixed-citation><mixed-citation xml:lang="en">Sian-Hulsmann J, Riederer P. The role of alpha-synuclein as  ferrireductase in  neurodegeneration associated with  Parkinson’s disease. J  Neural Transm (Vienna). 2020; 127(5): 749-754. doi: 10.1007/s00702-020-02192-0</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Abdeen AH, Trist BG, Double KL. Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis. NPJ Parkinsons Dis. 2022; 8(1): 83. doi: 10.1038/s41531-022-00345-4</mixed-citation><mixed-citation xml:lang="en">Abdeen  AH, Trist  BG, Double  KL. Empirical evidence for biometal dysregulation in Parkinson’s disease from a systematic review and Bradford Hill analysis. NPJ Parkinsons Dis. 2022; 8(1): 83. doi: 10.1038/s41531-022-00345-4</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Ayton S, Lei P, Hare DJ, Duce JA, George JL, Adlard PA, et al. Parkinson’s disease iron deposition caused by nitric oxide-induced loss of β-amyloid precursor protein. J Neurosci. 2015; 35(8): 3591- 3597. doi: 10.1523/JNEUROSCI.3439-14.2015</mixed-citation><mixed-citation xml:lang="en">Ayton S, Lei P, Hare DJ, Duce JA, George JL, Adlard PA, et al. Parkinson’s disease iron deposition caused by nitric oxide-induced loss of β-amyloid precursor protein. J Neurosci. 2015; 35(8): 3591- 3597. doi: 10.1523/JNEUROSCI.3439-14.2015</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Wong BX, Tsatsanis A, Lim LQ, Adlard PA, Bush AI, Duce JA. β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin. PLoS One. 2014; 9(12): e114174. doi: 10.1371/journal.pone.0114174</mixed-citation><mixed-citation xml:lang="en">Wong BX, Tsatsanis A, Lim LQ, Adlard PA, Bush AI, Duce JA. β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin. PLoS One. 2014; 9(12): e114174. doi: 10.1371/journal.pone.0114174</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Wang W, Zhang X, Gao Q, Xu H. TRPML1: An ion channel in the lysosome. Handb Exp Pharmacol. 2014; 222: 631-645. doi: 10.1007/978-3-642-54215-2_24</mixed-citation><mixed-citation xml:lang="en">Wang W, Zhang X, Gao Q, Xu H. TRPML1: An ion channel in  the  lysosome. Handb Exp Pharmacol. 2014; 222: 631-645. doi: 10.1007/978-3-642-54215-2_24</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Mills E, Dong XP, Wang F, Xu H. Mechanisms of brain iron transport: Insight into neurodegeneration and CNS disorders. Future Med Chem. 2010; 2(1): 51-64. doi: 10.4155/fmc.09.140</mixed-citation><mixed-citation xml:lang="en">Mills E, Dong XP, Wang F, Xu H. Mechanisms of brain iron transport: Insight into  neurodegeneration and  CNS disorders. Future Med Chem. 2010; 2(1): 51-64. doi: 10.4155/fmc.09.140</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Fonseca Ó, Ramos AS, Gomes LTS, Gomes MS, Moreira AC. New perspectives on circulating ferritin: Its role in health and disease. Molecules. 2023; 28(23): 7707. doi: 10.3390/molecules28237707</mixed-citation><mixed-citation xml:lang="en">Fonseca Ó, Ramos AS, Gomes LTS, Gomes MS, Moreira AC. New perspectives on circulating ferritin: Its role in health and disease. Molecules. 2023; 28(23): 7707. doi: 10.3390/molecules28237707</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Kawabata H. The mechanisms of systemic iron homeostasis and etiology, diagnosis, and treatment of hereditary hemochromatosis. Int J Hematol. 2018; 107(1): 31-43. doi: 10.1007/s12185-017-2365-3</mixed-citation><mixed-citation xml:lang="en">Kawabata  H. The  mechanisms of  systemic iron homeostasis and  etiology, diagnosis, and  treatment of  hereditary hemochromatosis. Int J Hematol. 2018; 107(1): 31-43. doi: 10.1007/s12185-017-2365-3</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Rhodes SL, Buchanan DD, Ahmed I, Taylor KD, Loriot MA, Sinsheimer JS, et al. Pooled analysis of iron-related genes in Parkinson’s disease: Association with transferrin. Neurobiol Dis. 2014; 62: 172-178. doi: 10.1016/j.nbd.2013.09.019</mixed-citation><mixed-citation xml:lang="en">Rhodes SL, Buchanan DD, Ahmed I, Taylor KD, Loriot MA, Sinsheimer JS, et al. Pooled analysis of iron-related genes in Parkinson’s disease: Association with transferrin. Neurobiol Dis. 2014; 62: 172-178. doi: 10.1016/j.nbd.2013.09.019</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Mastroberardino PG, Hoffman EK, Horowitz MP, Betarbet R, Taylor G, Cheng D, et al. A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson’s disease. Neurobiol Dis. 2009; 34(3): 417-431. doi: 10.1016/j.nbd.2009.02.009</mixed-citation><mixed-citation xml:lang="en">Mastroberardino  PG, Hoffman  EK, Horowitz  MP, Betarbet R, Taylor G, Cheng D, et al. A novel transferrin/TfR2-mediated mitochondrial iron transport system is  disrupted in  Parkinson’s disease. Neurobiol Dis. 2009; 34(3): 417-431. doi: 10.1016/j.nbd.2009.02.009</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Powers KM, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD, Checkoway H. Parkinson’s disease risks associated with dietary iron, manganese, and other nutrient intakes. Neurology. 2003; 60(11): 1761-1766. doi: 10.1212/01.wnl.0000068021.13945.7f</mixed-citation><mixed-citation xml:lang="en">Powers KM, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD, Checkoway H. Parkinson’s disease risks associated with dietary iron, manganese, and other nutrient intakes. Neurology. 2003; 60(11): 1761-1766. doi: 10.1212/01.wnl.0000068021.13945.7f</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Pichler I, Del Greco MF, Gögele M, Lill CM, Bertram L, Do CB, et al. Serum iron levels and the risk of Parkinson disease: A Mendelian randomization study. PLoS Med. 2013; 10(6): e1001462. doi: 10.1371/journal.pmed.1001462</mixed-citation><mixed-citation xml:lang="en">Pichler I, Del Greco MF, Gögele M, Lill CM, Bertram L, Do CB, et al. Serum iron levels and the risk of Parkinson disease: A Mendelian randomization study. PLoS Med. 2013; 10(6): e1001462. doi: 10.1371/journal.pmed.1001462</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Cheng P, Yu J, Huang W, Bai S, Zhu X, Qi Z, et al. Dietary intake of iron, zinc, copper, and risk of Parkinson’s disease: A metaanalysis. Neurol Sci. 2015; 36(12): 2269-2275. doi: 10.1007/s10072-015-2349-0</mixed-citation><mixed-citation xml:lang="en">Cheng P, Yu J, Huang W, Bai S, Zhu X, Qi Z, et al. Dietary intake of iron, zinc, copper, and risk of Parkinson’s disease: A metaanalysis. Neurol Sci. 2015; 36(12): 2269-2275. doi: 10.1007/s10072-015-2349-0</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Muñoz Y, Carrasco CM, Campos JD, Aguirre P, Núñez MT. Parkinson’s disease: The mitochondria-iron link. Parkinsons Dis. 2016; 2016: 7049108. doi: 10.1155/2016/7049108 55. Ramalingam M, Kim SJ. Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases. J Neural Transm (Vienna). 2012; 119(8): 891-910. doi: 10.1007/s00702-011-0758-7</mixed-citation><mixed-citation xml:lang="en">Muñoz Y, Carrasco CM, Campos JD, Aguirre P, Núñez MT. Parkinson’s disease: The  mitochondria-iron link. Parkinsons Dis. 2016; 2016: 7049108. doi: 10.1155/2016/7049108 55. Ramalingam M, Kim SJ. Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases. J  Neural Transm (Vienna). 2012; 119(8): 891-910. doi:  10.1007/s00702-011-0758-7</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Мезенцев Ю.А., Осипова О.А. Обзор современной информации о влиянии оксидативного стресса на преждевременное старение. Современные проблемы здравоохранения и медицинской статистики. 2022; 5: 249-269. doi: 10.24412/2312-2935-2022-5-249-269</mixed-citation><mixed-citation xml:lang="en">Mezentsev YuA, Osipova OA. Review of current information impact of oxidative stress on premature aging. Current Problems of Health Care and Medical Statistics. 2022; 5: 249-269. (In Russ.). doi: 10.24412/2312-2935-2022-5-249-269</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Bir A, Sen O, Anand S, Khemka VK, Banerjee P, Cappai R, et al. α-synuclein-induced mitochondrial dysfunction in isolated preparation and intact cells: Implications in the pathogenesis of Parkinson’s disease. J Neurochem. 2014; 131(6): 868-877. doi: 10.1111/jnc.12966</mixed-citation><mixed-citation xml:lang="en">Bir A, Sen O, Anand S, Khemka VK, Banerjee P, Cappai R, et al. α-synuclein-induced mitochondrial dysfunction in isolated preparation and intact cells: Implications in the pathogenesis of Parkinson’s disease. J Neurochem. 2014; 131(6): 868-877. doi: 10.1111/jnc.12966</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
