BiochemistryAssessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson’s disease: A pilot study
Introduction
Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder, being characterized by bradykinesia, tremor, rigidity, and postural instability [1]. PD affects about 1–2% of the worldwide population aged 55–65 years and greater than 3.5% subjects over 75 years of age [[2], [3], [4], [5], [6]]. Various factors including age-related changes, genetics, oxidative stress, pollutant exposure, etc. were shown to contribute to PD etiology [7,8]. The existing data also demonstrate a significant role of trace elements in PD pathogenesis [[9], [10], [11], [12], [13], [14]].
Earlier studies have demonstrated neurotoxic effect of copper, iron, and manganese and their related mechanisms [[15], [16], [17], [18], [19], [20]], whereas zinc has been shown to be both neurotoxic and neuroprotective depending upon the dose and disease status [[21], [22], [23]]. It has been hypothesized that metals are involved in neurodegeneration through modulation of protein aggregation (e.g. α-Synuclein) and fibril synthesis, oxidative stress, neuroinflammation, and excitotoxicity [15,[24], [25], [26]]. Interaction between metals and proteins of the nervous system is considered as one of the key factors for neurodegeneration [[27], [28], [29]]. Particularly, heavy metal exposure significantly up-regulates α-synuclein synthesis and aggregate formation being considered as one of the factors of the PD pathogenesis [30].
Multiple studies have assessed iron and copper levels in Parkinson’s disease. Particularly, a significant increase in iron deposits in substansia nigra and free copper serum levels in PD was associated with reduced ceruloplasmin content and ferroxidase activity [15]. Correspondingly, Kozlowski et al. (2012) demonstrated a significant elevation of copper and zinc levels in the cerebrospinal fluid (CSF) of PD patients [31]. Correspondingly, using metal chelation as a therapeutic strategy in the treatment of neurodegenerative diseases was shown to be rather effective and promising [[32], [33], [34]].
The pathogenetic role of manganese in PD development concomitant with alterations in the dopaminergic system is well established, along with excitotoxicity, neuroinflammation, and alterations in synaptic transmission [[35], [36], [37], [38]]. Specific symptoms of severe manganese overexposure known as manganism, are similar to those observed in PD [[39], [40], [41]].
At the same time the available data on the trace status in PD are rather contradictory. Therefore, the objective of our pilot study is to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) levels in hair, serum, urine of PD persons as well as determining the species of these metals in serum.
Section snippets
Sample collection
The research was performed in agreement with the ethical standards set in the Helsinki’s Declaration and its later amendments. The study protocol was approved by the Local Ethics Committee (I.M. Sechenov First Moscow State Medical University, Russia). A total of 13 patients with Parkinson’s disease (9 women and 4 men) and 14 gender-matched healthy subjects were enrolled in the current pilot study (Table 1). Mean age of female and male PD patients and controls was 76.4 ± 8.8 and 72.0 ± 6.8, and
Results and discussion
The obtained data demonstrate the relationship between PD and trace element levels in hair, urine, and serum (Table 2). Although no significant group differences in Cu, Fe, Mn, or Zn in the studied samples were revealed, a trend towards decreased hair (−22%) and urine (−41%) copper levels was observed in PD patients as compared to controls. At the same time, hair Fe and Mn levels tended to increase in PD, exceeding the control values by 24% and 21%, respectively. Urinary Fe and Zn levels were
Conflict of interest
The authors declare no conflict of interest
Acknowledgements
The study was performed in agreement with the plan of the studies of FSBSI FSC BST RAS № FNWZ-2019-0001. MA was supported in part by grants from the National Institute of Environmental Health Sciences. R01 ES10563, R01 ES07331, R01 ES020852, R21 ES025415.
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