{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:49:48Z","timestamp":1785498588673,"version":"3.56.0"},"reference-count":111,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Postencephalitic parkinsonism (PEP) is suggested to show a virus-induced pathology, which is different from classical idiopathic Parkinson\u2019s disease (PD) as there is no \u03b1-synuclein\/Lewy body pathology. However, PEP shows a typical clinical representation of motor disturbances. In addition, compared to PD, there is no iron-induced pathology. The aim of this preliminary study was to compare PEP with PD regarding iron-induced pathology, using histochemistry methods on paraffin-embedded post-mortem brain tissue. In the PEP group, iron was not seen, except for one case with sparse perivascular depositions. Rather, PEP offers a pathology related to tau-protein\/neurofibrillary tangles, with mild to moderate memory deficits only. It is assumed that this virus-induced pathology is due to immunological dysfunctions causing (neuro)inflammation-induced neuronal network disturbances as events that trigger clinical parkinsonism. The absence of iron deposits implies that PEP cannot be treated with iron chelators. The therapy with L-Dopa is also not an option, as L-Dopa only leads to an initial slight improvement in symptoms in isolated cases.<\/jats:p>","DOI":"10.3390\/cells13181511","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T03:16:51Z","timestamp":1725938211000},"page":"1511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Postencephalitic Parkinsonism: Unique Pathological and Clinical Features\u2014Preliminary Data"],"prefix":"10.3390","volume":"13","author":[{"given":"Sabrina","family":"Strobel","sequence":"first","affiliation":[{"name":"Institute of Pathology, Department of Neuropathology, University of Wuerzburg, 97080 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeswinder","family":"Sian-Hulsmann","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, University of Nairobi, P.O. Box 30197, Nairobi 00100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Tappe","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9641-7649","authenticated-orcid":false,"given":"Kurt","family":"Jellinger","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neurobiology, A-1150 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Riederer","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, 97080 Wuerzburg, Germany"},{"name":"Department of Psychiatry, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia-Maria","family":"Monoranu","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Department of Neuropathology, University of Wuerzburg, 97080 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s00702-023-02635-4","article-title":"The heterogeneity of Parkinson\u2019s disease","volume":"130","author":"Borghammer","year":"2023","journal-title":"J. Neural Transm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00702-019-02025-9","article-title":"\u03b1-Synuclein in Parkinson\u2019s disease: Causal or bystander?","volume":"126","author":"Riederer","year":"2019","journal-title":"J. Neural Transm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00702-008-0161-1","article-title":"Encephalitis lethargica and influenza. I. The role of the influenza virus in the influenza pandemic of 1918\/1919","volume":"116","author":"Foley","year":"2009","journal-title":"J. Neural Transm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1136\/jnnp-2019-322338","article-title":"Parkinson\u2019s disease: Etiopathogenesis and treatment","volume":"91","author":"Jankovic","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sian-Hulsmann, J., and Riederer, P. (2024). Virus-induced brain pathology and the neuroinflammation-inflammation continuum: The neurochemists view. J. Neural Transm., 1\u201325.","DOI":"10.1007\/s00702-023-02723-5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1073\/pnas.96.4.1651","article-title":"Origin and evolution of the 1918 \u201cSpanish\u201d influenza virus hemagglutinin gene","volume":"96","author":"Reid","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6785","DOI":"10.1073\/pnas.100140097","article-title":"Characterization of the 1918 \u201cSpanish\u201d influenza virus neuraminidase gene","volume":"97","author":"Reid","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cadar, D., Jellinger, K.A., Riederer, P., Strobel, S., Monoranu, C.M., and Tappe, D. (2021). No Metagenomic Evidence of Causative Viral Pathogens in Postencephalitic Parkinsonism Following Encephalitis Lethargica. Microorganisms, 9.","DOI":"10.3390\/microorganisms9081716"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s00702-022-02536-y","article-title":"Viruses, parkinsonism and Parkinson\u2019s disease: The past, present and future","volume":"129","author":"Leta","year":"2022","journal-title":"J. Neural Transm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s007020050086","article-title":"Postencephalitic parkinsonism\u2014A review","volume":"105","author":"Casals","year":"1998","journal-title":"J. Neural Transm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Donaldson, I., Marsden, C.D., Schneider, S.A., Bhatia, K.P., Donaldson, I., Marsden, C.D., Schneider, S., and Bhatia, K. (2012). Postencephalic parkinsonism. Marsden\u2019s Book of Movement Disorders, Oxford University Press.","DOI":"10.1093\/med\/9780192619112.001.0001"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/ana.410420312","article-title":"Pathological tau proteins in postencephalitic parkinsonism: Comparison with Alzheimer\u2019s disease and other neurodegenerative disorders","volume":"42","author":"Buee","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s007020050072","article-title":"PET study and neuropsychological assessment of a long-lasting post-encephalitic parkinsonism","volume":"105","author":"Cabaret","year":"1998","journal-title":"J. Neural Transm."},{"key":"ref_14","first-page":"22","article-title":"An immunohistochemical study of neurofibrillary tangle formation in post-encephalitic Parkinsonism","volume":"15","author":"Wong","year":"1996","journal-title":"Clin. Neuropathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/BF01285553","article-title":"Snpranuclear gaze palsy and eyelid apraxia in postencephalitic parkinsonism","volume":"104","author":"Wenning","year":"1997","journal-title":"J. Neural Transm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120013","DOI":"10.1016\/j.jns.2021.120013","article-title":"Editorial \u201cParkinsonism across the spectrum of movement disorders and beyond\u201d","volume":"433","author":"Jankovic","year":"2022","journal-title":"J. Neurol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s00702-019-02028-6","article-title":"Neuropathology and pathogenesis of extrapyramidal movement disorders: A critical update-I. Hypokinetic-rigid movement disorders","volume":"126","author":"Jellinger","year":"2019","journal-title":"J. Neural Transm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00401-009-0537-9","article-title":"Absence of alpha-synuclein pathology in postencephalitic parkinsonism","volume":"118","author":"Jellinger","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.bbadis.2008.08.001","article-title":"Viral parkinsonism","volume":"1792","author":"Jang","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/brain\/116.1.281","article-title":"Pathological overlap in cases of parkinsonism associated with neurofibrillary tangles. A study of recent cases of postencephalitic parkinsonism and comparison with progressive supranuclear palsy and Guamanian parkinsonism-dementia complex","volume":"116","author":"Geddes","year":"1993","journal-title":"Brain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1212\/WNL.59.4.645","article-title":"Alpha-synuclein studies are negative in postencephalic parkinsonism of von Economo","volume":"59","author":"Josephs","year":"2002","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/BF00691532","article-title":"Distribution and ultrastructure of Alzheimer\u2019s neurofibrillary tangles in postencephalitic Parkinsonism of Economo type","volume":"55","author":"Ishii","year":"1981","journal-title":"Acta Neuropathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/0304-3940(93)90589-D","article-title":"Anti-tau-positive glial fibrillary tangles in the brain of postencephalitic parkinsonism of Economo type","volume":"162","author":"Ikeda","year":"1993","journal-title":"Neurosci. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1440-1819.1996.tb01667.x","article-title":"A neuropathologic study of long-term, Economo-type postencephalitic parkinsonism with a prolonged clinical course","volume":"50","author":"Mizukami","year":"1996","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1093\/brain\/awx177","article-title":"Encephalitis lethargica: 100 years after the epidemic","volume":"140","author":"Hoffman","year":"2017","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0304-3940(92)90846-Y","article-title":"Distribution of neurofibrillary tangles and senile plaques in the cerebral cortex in postencephalitic parkinsonism","volume":"139","author":"Hof","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00702-021-02414-z","article-title":"Iron as the concert master in the pathogenic orchestra playing in sporadic Parkinson\u2019s disease","volume":"128","author":"Riederer","year":"2021","journal-title":"J. Neural Transm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0098-2997(00)00006-6","article-title":"The roles of iron in health and disease","volume":"22","author":"Lieu","year":"2001","journal-title":"Mol. Asp. Med."},{"key":"ref_29","first-page":"1426","article-title":"Ferroportin-mediated iron transport: Expression and regulation","volume":"1823","author":"Ward","year":"2012","journal-title":"BBA-Mol. Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nri3863","article-title":"Iron homeostasis in host defence and inflammation","volume":"15","author":"Ganz","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1182\/blood-2011-01-258467","article-title":"Hepcidin and iron regulation, 10 years later","volume":"117","author":"Ganz","year":"2011","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1079\/PNS19780022","article-title":"Iron-Deficiency and Neurotransmitter Synthesis and Function","volume":"37","author":"Youdim","year":"1978","journal-title":"Proc. Nutr. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.emc.2018.04.009","article-title":"Emergency Medicine Evaluation and Management of Anemia","volume":"36","author":"Long","year":"2018","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_34","first-page":"695","article-title":"Iron Overload in Patients with Chronic Liver Disease","volume":"12","author":"Kowdley","year":"2016","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3892\/ol.2021.12918","article-title":"Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma","volume":"22","author":"Yao","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.cca.2019.11.029","article-title":"Iron overload: Effects on cellular biochemistry","volume":"504","author":"Sousa","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_37","first-page":"251","article-title":"Selectivity of melaninized nigra-striatal dopamine neurons to degeneration in Parkinson\u2019s disease may depend on iron-melanin interaction","volume":"29","author":"Youdim","year":"1990","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1111\/j.1471-4159.1992.tb08362.x","article-title":"Iron-melanin complex in substantia nigra of parkinsonian brains: An X-ray microanalysis","volume":"59","author":"Jellinger","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/BF01244786","article-title":"Increased Iron (III) and Total Iron Content in Post-Mortem Substantia Nigra of Parkinsonian Brain","volume":"74","author":"Sofic","year":"1988","journal-title":"J. Neural Transm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1093\/brain\/114.4.1953","article-title":"Alterations in the Levels of Iron, Ferritin and Other Trace-Metals in Parkinsons-Disease and Other Neurodegenerative Diseases Affecting the Basal Ganglia","volume":"114","author":"Dexter","year":"1991","journal-title":"Brain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/jnr.490310214","article-title":"Regional Distribution of Iron and Iron-Regulatory Proteins in the Brain in Aging and Alzheimers-Disease","volume":"31","author":"Connor","year":"1992","journal-title":"J. Neurosci. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"120816","DOI":"10.1016\/j.jns.2023.120816","article-title":"Magnetic resonance imaging detection of deep gray matter iron deposition in multiple sclerosis: A systematic review","volume":"453","author":"Bisulca","year":"2023","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dusek, P., Hofer, T., Alexander, J., Roos, P.M., and Aaseth, J.O. (2022). Cerebral Iron Deposition in Neurodegeneration. Biomolecules, 12.","DOI":"10.3390\/biom12050714"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14802\/jmd.14034","article-title":"Neurodegeneration with brain iron accumulation: Diagnosis and management","volume":"8","author":"Hogarth","year":"2015","journal-title":"J. Mov. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.nbd.2015.02.007","article-title":"Neuroferritinopathy: From ferritin structure modification to pathogenetic mechanism","volume":"81","author":"Levi","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S1474-4422(14)70117-6","article-title":"The role of iron in brain ageing and neurodegenerative disorders","volume":"13","author":"Ward","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lee, J.H., and Lee, M.S. (2019). Brain Iron Accumulation in Atypical Parkinsonian Syndromes: In Vivo MRI Evidences for Distinctive Patterns. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00074"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.neuroimage.2009.05.006","article-title":"MRI estimates of brain iron concentration in normal aging: Comparison of field-dependent (FDRI) and phase (SWI) methods","volume":"47","author":"Pfefferbaum","year":"2009","journal-title":"Neuroimage"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1016\/j.neuroimage.2011.08.077","article-title":"MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping","volume":"59","author":"Bilgic","year":"2012","journal-title":"Neuroimage"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lee, S., and Kovacs, G.G. (2024). The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084269"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ficiara, E., Stura, I., and Guiot, C. (2022). Iron Deposition in Brain: Does Aging Matter?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710018"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zeng, W.Q., Cai, J., Zhang, L., and Peng, Q.W. (2024). Iron Deposition in Parkinson\u2019s Disease: A Mini-Review. Cell. Mol. Neurobiol., 44.","DOI":"10.1007\/s10571-024-01459-4"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/ene.13208","article-title":"Motor associations of iron accumulation in deep grey matter nuclei in Parkinson\u2019s disease: A cross-sectional study of iron-related magnetic resonance imaging susceptibility","volume":"24","author":"Loane","year":"2017","journal-title":"Eur. J. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"P1-078","DOI":"10.1212\/WNL.88.16_supplement.P1.078","article-title":"Powassan virus causing Post-encephalitic Parkinsonism","volume":"88","author":"Mittal","year":"2017","journal-title":"Neurology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/ana.20723","article-title":"Substantia nigra tangles are related to gait impairment in older persons","volume":"59","author":"Schneider","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s11910-018-0835-5","article-title":"Lewy Body Disease: Clinical and Pathological \u201cOverlap Syndrome\u201d between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease)","volume":"18","author":"Foguem","year":"2018","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jocn.2020.04.088","article-title":"Clinicopathological overlap of neurodegenerative diseases: A comprehensive review","volume":"78","author":"Das","year":"2020","journal-title":"J. Clin. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1474-4422(23)00404-0","article-title":"A biological classification of Parkinson\u2019s disease: The SynNeurGe research diagnostic criteria","volume":"23","author":"Hoglinger","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13195-014-0073-2","article-title":"Alpha-synuclein biology in Lewy body diseases","volume":"6","author":"Kim","year":"2014","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13024-019-0320-x","article-title":"\u03b1-synuclein in the pathophysiology of Alzheimer\u2019s disease","volume":"14","author":"Twohig","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s40478-018-0624-z","article-title":"The relevance of cerebrospinal fluid -synuclein levels to sporadic and familial Alzheimer\u2019s disease","volume":"6","author":"Twohig","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhang, X., Gao, F., Wang, D.D., Li, C., Fu, Y., He, W., and Zhang, J.M. (2018). Tau Pathology in Parkinson\u2019s Disease. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00809"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rawat, P., Sehar, U., Bisht, J., Selman, A., Culberson, J., and Reddy, P.H. (2022). Phosphorylated Tau in Alzheimer\u2019s Disease and Other Tauopathies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112841"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101619","DOI":"10.1016\/j.arr.2022.101619","article-title":"Oxidative stress: The core pathogenesis and mechanism of Alzheimer\u2019s disease","volume":"77","author":"Bai","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1179\/1351000213Y.0000000052","article-title":"Oxidative stress in Alzheimer\u2019s disease: Primary villain or physiological by-product?","volume":"18","author":"Sutherland","year":"2013","journal-title":"Redox Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1136\/jnnp.51.6.745","article-title":"The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson\u2019s disease","volume":"51","author":"Gibb","year":"1988","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/jnen\/62.4.389","article-title":"Colocalization of tau and alpha-synuclein epitopes in Lewy bodies","volume":"62","author":"Ishizawa","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-3-7091-6360-3_6","article-title":"Parkinson\u2019s disease\u2014A multifactorial neurodegenerative disorder","volume":"56","author":"Riess","year":"1999","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s004010050001","article-title":"Sequestration of iron by Lewy bodies in Parkinson\u2019s disease","volume":"100","author":"Castellani","year":"2000","journal-title":"Acta Neuropathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0006-2952(03)00293-4","article-title":"Iron-binding characteristics of neuromelanin of the human substantia nigra","volume":"66","author":"Double","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nrn1537","article-title":"Iron, brain ageing and neurodegenerative disorders","volume":"5","author":"Zecca","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00702-023-02630-9","article-title":"Lewy bodies, iron, inflammation and neuromelanin: Pathological aspects underlying Parkinson\u2019s disease","volume":"130","author":"Riederer","year":"2023","journal-title":"J. Neural Transm."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/ana.410350107","article-title":"Indexes of Oxidative Stress and Mitochondrial-Function in Individuals with Incidental Lewy Body Disease","volume":"35","author":"Dexter","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1111\/j.1471-4159.1989.tb07264.x","article-title":"Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson\u2019s disease","volume":"52","author":"Dexter","year":"1989","journal-title":"J. Neurochem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1471-4159.1991.tb08170.x","article-title":"Iron and aluminum increase in the substantia nigra of patients with Parkinson\u2019s disease: An X-ray microanalysis","volume":"56","author":"Hirsch","year":"1991","journal-title":"J. Neurochem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ma, L., Gholam Azad, M., Dharmasivam, M., Richardson, V., Quinn, R.J., Feng, Y., Pountney, D.L., Tonissen, K.F., Mellick, G.D., and Yanatori, I. (2021). Parkinson\u2019s disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies. Redox Biol., 41.","DOI":"10.1016\/j.redox.2021.101896"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40478-021-01145-2","article-title":"Cell specific quantitative iron mapping on brain slices by immuno-microPIXE in healthy elderly and Parkinson\u2019s disease","volume":"9","author":"Friedrich","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.nurt.2010.05.014","article-title":"Microglial Activation and Chronic Neurodegeneration","volume":"7","author":"Lull","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Ward, R.J., Dexter, D.T., and Crichton, R.R. (2022). Iron, Neuroinflammation and Neurodegeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137267"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuroscience.2017.08.023","article-title":"An Altered Blood-Brain Barrier Contributes to Brain Iron Accumulation and Neuroinflammation in the 6-Ohda Rat Model of Parkinson\u2019s Disease","volume":"362","author":"Marcellino","year":"2017","journal-title":"Neuroscience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1212\/WNL.38.8.1285","article-title":"Reactive Microglia Are Positive for Hla-Dr in the Substantia Nigra of Parkinsons and Alzheimers-Disease Brains","volume":"38","author":"Mcgeer","year":"1988","journal-title":"Neurology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/mds.21751","article-title":"Glial reactions in Parkinson\u2019s disease","volume":"23","author":"McGeer","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_83","first-page":"461","article-title":"The Role of Oxidative Stress in Parkinson\u2019s Disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Park. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41582-020-0312-z","article-title":"Perivascular spaces in the brain: Anatomy, physiology and pathology","volume":"16","author":"Wardlaw","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/ijs.12054","article-title":"Enlarged perivascular spaces and cerebral small vessel disease","volume":"10","author":"Potter","year":"2015","journal-title":"Int. J. Stroke"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s11682-019-00128-1","article-title":"Perivascular spaces in the centrum semiovale at the beginning of the 8th decade of life: Effect on cognition and associations with mineral deposition","volume":"14","author":"Ballerini","year":"2020","journal-title":"Brain Imaging Behav."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1093\/brain\/awn171","article-title":"Perivascular spaces\u2014MRI marker of inflammatory activity in the brain?","volume":"131","author":"Wuerfel","year":"2008","journal-title":"Brain"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41531-021-00155-0","article-title":"The role of brain perivascular space burden in early-stage Parkinson\u2019s disease","volume":"7","author":"Shen","year":"2021","journal-title":"npj Park. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Paul, G., and Elabi, O.F. (2022). Microvascular Changes in Parkinson\u2019s Disease-Focus on the Neurovascular Unit. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.853372"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2174\/1871527322666230330093829","article-title":"Blood-brain Barrier and Neurovascular Unit Dysfunction in Parkinson\u2019s Disease: From Clinical Insights to Pathogenic Mechanisms and Novel Therapeutic Approaches","volume":"23","author":"Khor","year":"2024","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/ana.20369","article-title":"Blood-brain barrier dysfunction in Parkinsonian midbrain in vivo","volume":"57","author":"Kortekaas","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/jcbfm.2015.32","article-title":"Striatal blood-brain barrier permeability in Parkinson\u2019s disease","volume":"35","author":"Gray","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Gasca-Salas, C., Pineda-Pardo, J.A., Del Alamo, M., Jimenez, T., Trompeta, C., Toltsis, G., Garcia-Canamaque, L., Fernandez-Rodriguez, B., Matarazzo, M., and Plaza de Las Heras, I. (2024). Nigrostriatal blood-brain barrier opening in Parkinson\u2019s disease. J. Neurol. Neurosurg. Psychiatry.","DOI":"10.1136\/jnnp-2023-332967"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.parkreldis.2022.06.004","article-title":"Biofluid markers of blood-brain barrier disruption and neurodegeneration in Lewy body spectrum diseases: A systematic review and meta-analysis","volume":"101","author":"Wong","year":"2022","journal-title":"Park. Relat. Disord."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ijbiomac.2022.12.134","article-title":"The impact of alpha-synuclein aggregates on blood-brain barrier integrity in the presence of neurovascular unit cells","volume":"229","author":"Hourfar","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Michalicova, A., Majerova, P., and Kovac, A. (2020). Tau Protein and Its Role in Blood-Brain Barrier Dysfunction. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.570045"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.parkreldis.2017.08.013","article-title":"Different iron deposition patterns in early- and middle-late-onset Parkinson\u2019s disease","volume":"44","author":"Xuan","year":"2017","journal-title":"Park. Relat. Disord."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF01217333","article-title":"Further experimental studies on the catecholamine metabolism in extrapyramidal diseases (Parkinson and chorea syndromes)","volume":"210","author":"Birkmayer","year":"1967","journal-title":"Arch Psychiatr. Nervenkr. (1970)"},{"key":"ref_99","first-page":"129","article-title":"Drug-Treatment of Parkinsons-Disease","volume":"311","author":"Quinn","year":"1995","journal-title":"Brit. Med. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.tips.2005.05.002","article-title":"The \u2018magic\u2019 of L-dopa: Why is it the gold standard Parkinson\u2019s disease therapy?","volume":"26","author":"Mercuri","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/jnnp.35.4.487","article-title":"Response of patients with postencephalitic Parkinsonism to levodopa","volume":"35","author":"Duvoisin","year":"1972","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/jnc.13572","article-title":"Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson\u2019s disease","volume":"139","author":"Duda","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Watanabe, H., Dijkstra, J.M., and Nagatsu, T. (2024). Parkinson\u2019s Disease: Cells Succumbing to Lifelong Dopamine-Related Oxidative Stress and Other Bioenergetic Challenges. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202401.0245.v1"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41531-020-00123-0","article-title":"COVID-19 and possible links with Parkinson\u2019s disease and parkinsonism: From bench to bedside","volume":"6","author":"Sulzer","year":"2020","journal-title":"npj Park. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1001\/archneurol.2010.135","article-title":"When Does Parkinson Disease Start?","volume":"67","author":"Savica","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.expneurol.2017.10.002","article-title":"Compensatory mechanisms in Parkinson\u2019s disease: Circuits adaptations and role in disease modification","volume":"298","author":"Blesa","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Turrigiano, G. (2012). Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a005736"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Clavaguera, F., Tolnay, M., and Goedert, M. (2017). The Prion-Like Behavior of Assembled Tau in Transgenic Mice. Cold Spring Harb. Perspect. Biol., 7.","DOI":"10.1101\/cshperspect.a024372"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Jan, A., Goncalves, N.P., Vaegter, C.B., Jensen, P.H., and Ferreira, N. (2021). The Prion-Like Spreading of Alpha-Synuclein in Parkinson\u2019s Disease: Update on Models and Hypotheses. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158338"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1007\/s13311-022-01316-6","article-title":"Metformin Attenuates Tau Pathology in Tau-Seeded PS19 Mice","volume":"20","author":"Zhao","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.neuropharm.2017.08.015","article-title":"Metformin lowers \u03b1-synuclein phosphorylation and upregulates neurotrophic factor in the MPTP mouse model of Parkinson\u2019s disease","volume":"125","author":"Katila","year":"2017","journal-title":"Neuropharmacology"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/18\/1511\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:52:34Z","timestamp":1760111554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/18\/1511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,10]]},"references-count":111,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["cells13181511"],"URL":"https:\/\/doi.org\/10.3390\/cells13181511","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,10]]}}}