A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson’s Disease and Parkinsonian Mice

Bogdanov, Vsevolod; Kim, A. R.; Nodel, M. R.; Павленко, Т. А.; Pavlova, Ekaterina; Блохин, В. Е.; Чеснокова, Н. Б.; Ugrumov, M. V.

doi:10.3390/ijms22094736

Cited by 13 publications

(11 citation statements)

References 65 publications

(121 reference statements)

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“…Recently, we have proposed a third, hybrid approach to the development of the preclinical diagnosis of PD. It is based on a search for biomarkers in untreated PD patients at an early clinical stage, and in animal models of the preclinical and early clinical stages of PD [5,20,22]. In such case, only those changes in body fluids that are characteristic of both patients and animal models are considered as biomarkers of the preclinical stage.…”

Section: Introductionmentioning

confidence: 99%

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

Katunina

Блохин

Nodel

et al. 2023

IJMS

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Parkinson’s disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in the lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (LAG3), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (PARK7), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD.

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Section: Introductionmentioning

confidence: 99%

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

Katunina

Блохин

Nodel

et al. 2023

IJMS

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“…Therefore, it seems justified to study the change in the profile of monoamine accumulation in tears as a potential source of PD biomarkers. Bogdanov et al (2021) [ 82 ] analyzed the change in the concentration of selected catecholamines (dopamine, noradrenaline, adrenaline), metabolites: L-DOPA (dopamine precursor) and DOPAC (dopamine degradation product). The study also analyzed the content of α-2-macroglobulin, which is a proteases inhibitor present in patients’ PD tears and involved in the pathogenesis of PD [ 82 ].…”

Section: Resultsmentioning

confidence: 99%

“…Bogdanov et al (2021) [ 82 ] analyzed the change in the concentration of selected catecholamines (dopamine, noradrenaline, adrenaline), metabolites: L-DOPA (dopamine precursor) and DOPAC (dopamine degradation product). The study also analyzed the content of α-2-macroglobulin, which is a proteases inhibitor present in patients’ PD tears and involved in the pathogenesis of PD [ 82 ]. The change in the regulation of this protein is observed in the CSF of people with PD [ 83 ].…”

Section: Resultsmentioning

confidence: 99%

“…Lactotransferin, clusterin, and beta-2-microglobulin were indicated in the group of immune response-related proteins with a high prognostic value. The authors note that these were a pilot study and that the analyses should be repeated in a larger population to validate them [ 82 ]. A valuable supplement to the knowledge about the PD substrate are the results of Acer et al (2022) [ 17 ], where authors are already jumping on protein candidates in the pre-clinical phase of PD.…”

Section: Resultsmentioning

confidence: 99%

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Tear Biomarkers in Alzheimer’s and Parkinson’s Diseases, and Multiple Sclerosis: Implications for Diagnosis (Systematic Review)

Król-Grzymała

Sienkiewicz-Szłapka

Fiedorowicz

et al. 2022

IJMS

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Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015–2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.

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“…This is due to the fact that MPTP is converted in the body into MPP+, a toxin of catecholaminergic neurons, which causes the death of these neurons in the brain, as well as in the peripheral nervous system in animals, which is also typical for patients [ 29 ]. Our MPTP models of PD at the preclinical and clinical stages were developed 10 years ago [ 28 ] and then used to assess the stage-dependent molecular mechanisms of neurodegeneration and neuroplasticity in the nigrostriatal dopaminergic system [ 25 , 30 , 31 ], as well as the peripheral manifestations of these processes [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

et al. 2022

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Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

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A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson’s Disease and Parkinsonian Mice

Cited by 13 publications

References 65 publications

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

Tear Biomarkers in Alzheimer’s and Parkinson’s Diseases, and Multiple Sclerosis: Implications for Diagnosis (Systematic Review)

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

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