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Development of differential and early (preclinical) diagnostics of Parkinson’s disease (PD) is among the priorities in neuroscience. We searched for changes in the level of catecholamines and α-2-macroglobulin activity in the tear fluid (TF) in PD patients at an early clinical stage. It was shown that TF in patients is characterized by an increased...
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... the TF of PD patients, but only on the side of pronounced motor disorders (ipsilateral side), we found an increase in the concentration and content of noradrenaline compared to the control ( Table 3). Considering that adrenergic receptors are expressed in the cells of the conjunctiva and cornea facing the TF [54,55], an increase in the level of noradrenaline in the TF can be a compensatory mechanism under their desympathization associated with PD ( Figure 6). In addition, we found a decrease in the concentration and content of adrenaline in the TF of PD patients, both in the ipsilateral and contralateral sides (Table 3). ...
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... addition, we found a decrease in the concentration and content of adrenaline in the TF of PD patients, both in the ipsilateral and contralateral sides (Table 3). These data are difficult to interpret, although it is possible that adrenaline enters the TF from the blood (Figure 6), overcoming a blood-tear barrier, which becomes more permeable in pathology [56]. Data on the contrasting changes in the level of noradrenaline-an increase in the TF and a decrease in the plasma [14,15], respectively-attract special attention (Table 3). ...
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... for the interpretation of these data, one should proceed from the idea that the noradrenaline concentration in body fluids is an integral indicator of the complementary processes, neurodegeneration and neuroplasticity. This means that an increased level of noradrenaline in TF can suggest the local prevalence of compensatory processes over neurodegeneration ( Figure 6). A decreased level of noradrenaline in the blood can be an indicator of the systemic prevalence of neurodegeneration over neuroplasticity. ...
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... have shown for the first time that in PD patients, the activity of α-2-macroglobulin is almost doubled. Interestingly, in contrast to the asymmetric change in the noradrenaline level in the TF, the change in α-2-macroglobulin activity is symmetrical ( Figure 6). This is probably due to the fact that even with asymmetric degradation of catecholaminergic systems, at least of the nigrostriatal dopaminergic system [45], the pathogenesis of PD is characterized by general symmetric manifestations, such as neuroinflammation, circulation of aggregated α-synuclein, and neuroplasticity. ...
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... is probably due to the fact that even with asymmetric degradation of catecholaminergic systems, at least of the nigrostriatal dopaminergic system [45], the pathogenesis of PD is characterized by general symmetric manifestations, such as neuroinflammation, circulation of aggregated α-synuclein, and neuroplasticity. α-2-macroglobulin is involved in the regulation of these asymmetric processes ( Figure 6) [24]. A significant increase in the activity of α-2-macroglobulin in the TF was also shown in mice in the model of the preclinical stage of PD and, to an even greater extent, in the model of the clinical stage of PD. ...
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... the wide variety of α-2-macroglobulin functions, it is difficult to unambiguously interpret the changes in its activity that we found in PD patients and in animal models of PD ( Figure 6). Indeed, these changes can be the result of the α-2-macroglobulin ability to inhibit proteolytic enzymes, bind cytokines, growth factors, apolipoproteins, and other proteins, which can be associated with PD [60]. ...
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... the TF of PD patients, but only on the side of pronounced motor disorders (ipsilateral side), we found an increase in the concentration and content of noradrenaline compared to the control ( Table 3). Considering that adrenergic receptors are expressed in the cells of the conjunctiva and cornea facing the TF [54,55], an increase in the level of noradrenaline in the TF can be a compensatory mechanism under their desympathization associated with PD ( Figure 6). In addition, we found a decrease in the concentration and content of adrenaline in the TF of PD patients, both in the ipsilateral and contralateral sides (Table 3). ...
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... addition, we found a decrease in the concentration and content of adrenaline in the TF of PD patients, both in the ipsilateral and contralateral sides (Table 3). These data are difficult to interpret, although it is possible that adrenaline enters the TF from the blood (Figure 6), overcoming a blood-tear barrier, which becomes more permeable in pathology [56]. Data on the contrasting changes in the level of noradrenaline-an increase in the TF and a decrease in the plasma [14,15], respectively-attract special attention (Table 3). ...
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... for the interpretation of these data, one should proceed from the idea that the noradrenaline concentration in body fluids is an integral indicator of the complementary processes, neurodegeneration and neuroplasticity. This means that an increased level of noradrenaline in TF can suggest the local prevalence of compensatory processes over neurodegeneration ( Figure 6). A decreased level of noradrenaline in the blood can be an indicator of the systemic prevalence of neurodegeneration over neuroplasticity. ...
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... have shown for the first time that in PD patients, the activity of α-2-macroglobulin is almost doubled. Interestingly, in contrast to the asymmetric change in the noradrenaline level in the TF, the change in α-2-macroglobulin activity is symmetrical ( Figure 6). This is probably due to the fact that even with asymmetric degradation of catecholaminergic systems, at least of the nigrostriatal dopaminergic system [45], the pathogenesis of PD is characterized by general symmetric manifestations, such as neuroinflammation, circulation of aggregated α-synuclein, and neuroplasticity. ...
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... is probably due to the fact that even with asymmetric degradation of catecholaminergic systems, at least of the nigrostriatal dopaminergic system [45], the pathogenesis of PD is characterized by general symmetric manifestations, such as neuroinflammation, circulation of aggregated α-synuclein, and neuroplasticity. α-2-macroglobulin is involved in the regulation of these asymmetric processes ( Figure 6) [24]. A significant increase in the activity of α-2-macroglobulin in the TF was also shown in mice in the model of the preclinical stage of PD and, to an even greater extent, in the model of the clinical stage of PD. ...
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... the wide variety of α-2-macroglobulin functions, it is difficult to unambiguously interpret the changes in its activity that we found in PD patients and in animal models of PD ( Figure 6). Indeed, these changes can be the result of the α-2-macroglobulin ability to inhibit proteolytic enzymes, bind cytokines, growth factors, apolipoproteins, and other proteins, which can be associated with PD [60]. ...
Citations
... Conversely, lower levels of dodecenoylcarnitine, tetradecenoylcarnitine, and 3-hydroxy-octadecenoylcarnitine were observed. Additionally, higher [180] CCL2 [181] Proteins linked to inflammation and neurodegeneration, apoptosis, and immune reactions [182] MMP-9, ApoD [182] α-2-macroglobulin [183] Adrenaline, noradrenaline [183] Norepinephrine, dopamine, epinephrine [184] Breast cancer Proteins involved in immune response pathways and metabolic cascades [185,186] Collagen [187] Carotenoids [187] miR-21 and miR-200c (in tear exosomes) [188] Eye cancer Cystatin C, LTF [189] Colon, prostate, lung, ovarian cancer Lacryglobin [190] serotonin levels were detected in tears of MuS patients compared to healthy controls and glaucoma patients, suggesting its involvement in the inflammatory pathogenesis of MuS through de novo ceramide synthesis [16]. ...
... Conversely, lower levels of dodecenoylcarnitine, tetradecenoylcarnitine, and 3-hydroxy-octadecenoylcarnitine were observed. Additionally, higher [180] CCL2 [181] Proteins linked to inflammation and neurodegeneration, apoptosis, and immune reactions [182] MMP-9, ApoD [182] α-2-macroglobulin [183] Adrenaline, noradrenaline [183] Norepinephrine, dopamine, epinephrine [184] Breast cancer Proteins involved in immune response pathways and metabolic cascades [185,186] Collagen [187] Carotenoids [187] miR-21 and miR-200c (in tear exosomes) [188] Eye cancer Cystatin C, LTF [189] Colon, prostate, lung, ovarian cancer Lacryglobin [190] serotonin levels were detected in tears of MuS patients compared to healthy controls and glaucoma patients, suggesting its involvement in the inflammatory pathogenesis of MuS through de novo ceramide synthesis [16]. ...
... Bogdanov et al. conducted a study analyzing the concentration of selected catecholamines (dopamine, noradrenaline, adrenaline) and metabolites (3,4-dihydroxy-L-phenylalanine and 3,4-dihydroxyphenylacetic acid, known as L-DOPA and DOPAC) in tears of patients with PD [183]. The study also investigated the presence of α-2-macroglobulin, a protease inhibitor associated with PD pathogenesis and observed in the CSF of PD patients. ...
... Further studies of the same group revealed that TF norepinephrine is elevated mainly on the ipsilateral side of pronounced motor symptoms. A decrease in the level of adrenaline and α-2-macroglobulin on both sides was found in comparison with the control group [133]. The levels of total α-synuclein (decreased) and oligomeric synuclein (increased) are potentially different in the TF of patients with PD and healthy people in the control group, while the increase in oligomeric synuclein does not depend on the stage of PD. ...
The simplicity of collecting and evaluating tear fluid (TF) can potentially provide a convenient non-invasive diagnostic tool that easily fits into a personalized approach to medicine based on risk assessment. Though, to date, most tear biomarkers are not yet ready for routine use due to problems with their clinical validation, given the huge clinical advantage of TF and the emerging advanced technical approaches developed for proteomic, lipidomic and metabolomic analysis of tears, TF studies will doubtless become a routine test for health monitoring in the near future. A number of associations between the levels of different substances in TF and the brain makes TF an invaluable source of brain disease biomarkers helpful in early diagnostics and personalized treatment. TF is a promising biological material, an invaluable source for pre-dictive, diagnostic, prognostic, and mechanistic biomarkers.
... Indeed, imbalances in the Trp-KYN pathway were suspected of causing neurodegeneration due to a heightened ratio of neurotoxic to neuroprotective metabolites, such as the reported increase in quinolinic acid (QUIN) in blood plasma and 3hydroxykynurenine (3-HK) in the cerebrospinal fluid of PD patients, which was implicated to increased oxidative stress, excitotoxicity, and neuroinflammation where dopaminergic neurons were particularly vulnerable [17,21,22]. Since dopamine is a precursor of other catecholamines, specifically epinephrine and norepinephrine, other non-motor functionssuch as peristalsis, heart rate, and blood pressure regulation-are diminished for PD patients [10,[23][24][25]. Gnanaraj et al. [8] summarized the PD-relevant proteins of utmost concern for their symptomatic treatment and neuroprotection. ...
Parkinson’s disease (PD) is one of the large-scale health issues detrimental to human quality of life, and current treatments are only focused on neuroprotection and easing symptoms. This study evaluated in silico binding activity and estimated the stability of major metabolites in the roots of R. palmatum (RP) with main protein targets in Parkinson’s disease and their ADMET properties. The major metabolites of RP were subjected to molecular docking and QSAR with α-synuclein, monoamine oxidase isoform B, catechol o-methyltransferase, and A2A adenosine receptor. From this, emodin had the greatest binding activity with Parkinson’s disease targets. The chemical stability of the selected compounds was estimated using density functional theory analyses. The docked compounds showed good stability for inhibitory action compared to dopamine and levodopa. According to their structure–activity relationship, aloe-emodin, chrysophanol, emodin, and rhein exhibited good inhibitory activity to specific targets. Finally, mediocre pharmacokinetic properties were observed due to unexceptional blood–brain barrier penetration and safety profile. It was revealed that the major metabolites of RP may have good neuroprotective activity as an additional hit for PD drug development. Also, an association between redox-mediating and activities with PD-relevant protein targets was observed, potentially opening discussion on electrochemical mechanisms with biological functions.
... 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. ...
... 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. Our recent comparative analysis of blood and tear fluid biomarkers in untreated patients at the early clinical stage of PD and in animal models of PD have shown that no more than 25% of biomarkers found in patients can be considered as preclinical biomarkers [20,22]. ...
... In this study, we assessed changes in 29 blood parameters in patients at risk. They were selected for analysis, taking into account the peculiarities of the pathogenesis of PD and previously obtained data on PD biomarkers found in untreated patients at an early clinical stage of PD [20,22,[52][53][54]. ...
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.
... Then, tear fluid components from both eyes from a mouse were eluted for 20 min with saline (50 µL) in one tube, centrifuged for 10 min at 3000 rpm, and the supernatant was used for testing. In the tear fluid eluate, the protein concentration was determined according to Lowry [31], and the activity of α2-MG was determined by the enzymatic method with the specific substrate N-benzoyl-DL-arginine-p-nitroanilide (BAPN), as described previously [32]. The activity of α2-MG was expressed as nmol/min × mL of tear fluid and nmol/min × mg of protein. ...
... One of the markers of a neurodegenerative process, not only in the retina but also in the brain is an increase in the level of α2-MG in the tear fluid [32]. α2-MG is a protein of acute phase inflammation, an inhibitor of a wide range of proteolytic enzymes, and a regulator of the function of many cytokines and growth factors. ...
Dysregulation of intraocular pressure (IOP) is one of the main risk factors for glaucoma. γ-synuclein is a member of the synuclein family of widely expressed synaptic proteins within the central nervous system that are implicated in certain types of neurodegeneration. γ-synuclein expression and localization changes in the retina and optic nerve of patients with glaucoma. However, the mechanisms by which γ-synuclein could contribute to glaucoma are poorly understood. We assessed the presence of autoantibodies to γ-synuclein in the blood serum of patients with primary open-angle glaucoma (POAG) by immunoblotting. A positive reaction was detected for five out of 25 patients (20%) with POAG. Autoantibodies to γ-synuclein were not detected in a group of patients without glaucoma. We studied the dynamics of IOP in response to IOP regulators in knockout mice (γ-KO) to understand a possible link between γ-synuclein dysfunction and glaucoma-related pathophysiological changes. The most prominent decrease of IOP in γ-KO mice was observed after the instillation of 1% phenylephrine and 10% dopamine. The total protein concentration in tear fluid of γ-KO mice was approximately two times higher than that of wild-type mice, and the activity of neurodegeneration-linked protein α2-macroglobulin was reduced. Therefore, γ-synuclein dysfunction contributes to pathological processes in glaucoma, including dysregulation of IOP.
... Bogdanov et al. [39] analyzed the change in the tear concentration of selected catecholamines (dopamine, noradrenaline, adrenaline) and α-2-macroglobulin, a protease inhibitor involved in the pathogenesis of PD. It was shown that tears in PD patients are characterized by an increased level of noradrenaline mainly on the ipsilateral side of pronounced motor symptoms, a decreased level of adrenaline on both sides, and an increased α-2-macroglobulin activity on both sides compared to controls. ...
Parkinson disease (PD) is a progressive, neurodegenerative disease of the central nervous system. Visual disturbance is one of the most frequent nonmotor abnormalities referred to by patients suffering from PD at early stages. Furthermore, ocular surface alterations including mainly dry eye and blink reduction represent another common finding in patients with PD. Tears of PD patients show specific alterations related to protein composition, and in vivo confocal microscopy has demonstrated profound changes in different corneal layers in this setting. These changes can be attributed not only to the disease itself, but also to the medications used for its management. In particular, signs of corneal toxicity, both at epithelial and endothelial level, are well described in the literature in PD patients receiving amantadine. Management of PD patients from the ophthalmologist’s side requires knowledge of the common, but often underdiagnosed, ocular surface alterations as well as of the signs of drug toxicity. Furthermore, ocular surface biomarkers can be useful for the early diagnosis of PD as well as for monitoring the degree of neural degeneration over time.
... 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]. ...
... 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]. ...
... 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]. ...
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.
... Cependant, ces échantillons présentent une stabilité du métabolome moins importante que le sang, ce qui rend ainsi leur utilisation moins fiable (Stevens et al., 2019). De façon plus surprenante, d'autres types d'échantillons tels que le liquide lacrymal ou le sébum ont récemment été étudiés pour le diagnostic de la MP et, bien qu'ils restent inférieurs aux résultats des études se basant sur les échantillons de sang, ils montrent des résultats encourageants avec une spécificité entre 66 et 87% (Bogdanov et al., 2021;Sinclair et al., 2021). ...
La maladie de Parkinson (MP) est une pathologie neurodégénérative caractérisée par la perte progressive des neurones dopaminergiques de la substantia nigra pars compacta (SNc). Malgré une avancée considérable des traitements proposés aux patients, la MP reste à ce jour toujours incurable. Les deux principaux facteurs qui expliquent cet échec thérapeutique sont : i) une compréhension incomplète de la physiopathologie de la MP, et ii) son diagnostic tardif.En effet, celui-ci est basé sur l’évaluation de symptômes moteurs caractéristiques de la maladie qui apparaissent alors que le processus neurodégénératif est déjà très avancé (50-60% des neurones de la SNc sont déjà morts). Pourtant, il a été montré que les patients atteints de la MP peuvent également présenter des troubles neuropsychiatriques qui apparaissent avant les symptômes moteurs et même dès les phases précoces de la maladie.De manière intéressante, des altérations du métabolisme cérébral, mais également du métabolisme sanguin, ont été identifiées chez des patients atteints de la MP, et chez des patients présentant des symptômes neuropsychiatriques semblables à ceux observés chez les patients parkinsoniens. A ce jour, aucune étude métabolique ne s’est intéressée spécifiquement aux troubles neuropsychiatriques et à la MP de façon conjointe. La comparaison du profil métabolique à différents stades de la pathologie, et notamment dès les phases précoces, pourrait non seulement servir d’outil diagnostic, mais également permettre d’identifier des cibles pertinentes pour le développement de stratégies thérapeutiques.Dans ce contexte, l’objectif de ma thèse a été d’étudier les altérations du métabolisme associées aux différentes phases de la maladie, et notamment aux phases précoces. L’originalité de cette étude repose sur l’utilisation d’échantillons provenant de plusieurs modèles animaux mais également de patients. Ainsi, nous avons conduit des études de métabolomique par résonance magnétique nucléaire (RMN) sur des échantillons de sérum provenant des modèles de rat 6-OHDA, rat alpha-synucléine et de primate non-humain MPTP, mimant différents stades de la maladie, ainsi qu’à partir d’échantillons sanguins provenant de 3 cohortes de patients nouvellement diagnostiqués.La comparaison des dérégulations métaboliques observées chez l’animal et chez l’humain dans le sérum nous a permis de développer un biomarqueur capable de séparer les patients nouvellement diagnostiqués des contrôles avec une grande fiabilité. De même, nous avons montré que notre biomarqueur permettait de clairement séparer les animaux mimant les phases précoces des animaux mimant les phases plus tardives, suggérant ainsi qu’il pourrait être utilisé pour un diagnostic très précoce de la MP.Des dérégulations communes au niveau sanguin et cérébral nous ont permis d’émettre des hypothèses mécanistiques quant à la physiopathologie de la MP.Notamment, des altérations associées au métabolisme du pyruvate ont particulièrement retenu notre attention, compte tenu de son implication dans le métabolisme énergétique qui est fortement impacté dans la maladie. Celles-ci nous ont conduit à formuler l’hypothèse que le pyruvate ne serait plus utilisé comme source énergétique préférentielle au sein de la cellule, possiblement à cause d’un blocage au niveau de l’entrée dans la mitochondrie. Pour tester cette hypothèse, nous avons bloqué chez des rats normaux le transporteur mitochondrial du pyruvate (MPC), qui est le seul point d'entrée du pyruvate dans la matrice mitochondriale et joue un rôle crucial dans le métabolisme énergétique. Ainsi, nous avons pu mettre en évidence que le blocage du MPC entraîne une redirection de la production d'énergie cellulaire au profit d’autres sources comme les lipides et les acides aminés. Cette redirection s’accompagnait d’une atténuation des atteintes cellulaire et comportementale chez le rat 6-OHDA, mettant ainsi en lumière les capacités neuroprotectrices du blocage du MPC pour la MP.
... 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]. ...
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.
