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      The potential significance of hepcidin evaluation in progressive supranuclear palsy

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          Abstract

          Introduction

          Hepcidin is a peptide associated with controlling the distribution of iron in tissues. Growing interest is linked with its impact on neurodegenerative diseases, as disruption of the iron regulation may be considered an initiatory element of pathological protein accumulation. The possible impact of hepcidin was not previously sufficiently explored in progressive supranuclear palsy (PSP).

          Methods

          Twelve patients with PSP–Richardson's syndrome (PSP–RS), 12 with PSP‐Parkinsonism Predominant (PSP‐P), and 12 controls were examined using Unified Parkinson's Disease Rating Scale—III part (UPDRS‐III) in OFF stage and analyzed in the context of hepcidin levels in the serum.

          Results

          The work revealed increased levels of hepcidin in PSP–RS when compared to PSP‐P and controls. Moreover, hepcidin was found to be negatively correlated with UPDRS‐III results in PSP–RS, whereas positively in PSP‐P.

          Conclusion

          The work may suggest a possible impact of hepcidin in PSP, possibly differing depending on its subtype.

          Abstract

          The association between hepcidin levels and parkinsonian syndrome in Progressive Supranuclear Palsy subtypes.

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          Most cited references18

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          Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.

          PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome.
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            Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFalpha, and INFgamma concentrations are elevated in patients with atypical and idiopathic parkinsonism.

            We investigated serum levels of interleukin (IL)-2, IL-10, IL-6, IL-4, TNFalpha, INFgamma in 7 patients with atypical parkinsonism (AP), 31 idiopathic PD (iPD) patients, 17 idiopathic PD with cardiovascular risk factor (iPD-CVRF) patients, and 20 age-matched controls (healthy, non-parkinsonian patients). Cytokine concentrations were measured using the Becton Dickinson (BD) human Th1/Th2 Cytokine kit II with a flow cytometry system. The concentrations of IL-2, IL-10, IL-4, IL-6, TNFalpha, and INFgamma were detectable in the serum from all groups, including the control. Increased serum IL-2, IL-10, IL-4, IL-6, TNFalpha, and INFgamma concentrations were found in all groups of parkinsonian patients, as compared to the control group. The highest elevations of serum IL-2, IL-4, IL-6, TNFalpha, and INFgamma concentrations were observed in AP patients, as compared to the iPD and iPD-CVRF groups. However, the serum IL-6 concentration was higher in the iPD-CVRF group than in the iPD group. The IL-10 level was significantly higher in all groups of PD patients relative to the control group, but was the lowest in the serum from the AP patients. Moreover, the serum levels of lipid peroxidation products were enhanced 2.1- and 1.5-fold in AP and both iPD groups, respectively. These results argue in favor of the involvement of immunological events in the process of neurodegeneration in AP and PD.
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              Metal Dyshomeostasis and Inflammation in Alzheimer's and Parkinson's Diseases: Possible Impact of Environmental Exposures

              A dysregulated metal homeostasis is associated with both Alzheimer's (AD) and Parkinson's (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering of cortex copper mechanism is suggested. An age-related mild chronic inflammation and/or elevated intracellular iron can trigger hepcidin production followed by its binding to ferroportin which is the only neuronal iron exporter, thereby subjecting it to lysosomal degradation. Subsequently raised neuronal iron levels can induce translation of the ferroportin assisting and copper binding amyloid precursor protein (APP); constitutive APP transmembrane passage lowers the copper pool which is important for many enzymes. Using in silico gene expression analyses, we here show significantly decreased expression of copper-dependent enzymes in AD brain and metallothioneins were upregulated in both diseases. Although few AD exposure risk factors are known, AD-related tauopathies can result from cyanobacterial microcystin and β -methylamino-L-alanine (BMAA) intake. Several environmental exposures may represent risk factors for PD; for this disease neurodegeneration is likely to involve mitochondrial dysfunction, microglial activation, and neuroinflammation. Administration of metal chelators and anti-inflammatory agents could affect disease outcomes.
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                Author and article information

                Contributors
                piotr.alster@wum.edu.pl
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                21 June 2024
                June 2024
                : 14
                : 6 ( doiID: 10.1002/brb3.v14.6 )
                : e3552
                Affiliations
                [ 1 ] Department of Neurology Medical University of Warsaw Warsaw Poland
                [ 2 ] Department of Biochemistry Medical University of Warsaw Warsaw Poland
                [ 3 ] Department of Infectious and Tropical Diseases and Hepatology Medical University of Warsaw Warsaw Poland
                Author notes
                [*] [* ] Correspondence

                Piotr Alster, Department of Neurology, Medical University of Warsaw, Kondratowicza str. 8, 03‐242 Warsaw, Poland.

                Email: piotr.alster@ 123456wum.edu.pl

                Author information
                https://orcid.org/0000-0002-5371-6817
                Article
                BRB33552
                10.1002/brb3.3552
                11191750
                90e96b63-6874-4229-b4aa-9ab42a47b1ac
                © 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 March 2024
                : 16 November 2023
                : 19 March 2024
                Page count
                Figures: 3, Tables: 1, Pages: 5, Words: 2845
                Funding
                Funded by: Warszawski Uniwersytet Medyczny , doi 10.13039/501100004166;
                Award ID: MB/M/09[16]
                Categories
                Brief Report
                Brief Report
                Custom metadata
                2.0
                June 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.4 mode:remove_FC converted:21.06.2024

                Neurosciences
                atypical parkinsonism,hepcidin,progressive supranuclear palsy,psp
                Neurosciences
                atypical parkinsonism, hepcidin, progressive supranuclear palsy, psp

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