natriuretic-peptide--c-type and Parkinson-Disease

C-type Natriuretic Peptide is a neuropeptide widely expressed in the central nervous system including dopaminergic neurons projecting to basal ganglia. Previous work shows that concentrations of the peptide in cerebrospinal fluid are depressed in drug naïve PD subjects, decline over time and can be restored by doses of monoamine oxidase inhibitors that delay the need for levodopa. Whether plasma levels are similarly depressed in drug naïve subjects, or affected by dopaminergic drugs, is unknown. Our objectives were to determine whether (i) peptide products in plasma differ from normal in PD, and (ii) levels are affected by dopaminergic treatment.. Plasma C-type Natriuretic Peptide and amino-terminal proCNP were measured in two groups - 27 drug naïve subjects with PD, and 30 subjects stabilized on dopaminergic drugs for at least 3 years. Values were compared with standard deviation scores from a population reference group without neurological disorder. Independent associations with predetermined variables known to affect plasma concentrations were assessed by multivariate analysis.. In both PD groups, plasma amino-terminal proCNP was significantly depressed compared to the reference range. Concentrations did not differ between the two groups. No correlation with disease duration or phenotype was found. Across all subjects, in a model initially comprising 7 factors, serum creatinine, PD and age were independent significant associations with amino-terminal proCNP.. Plasma concentrations of amino-terminal proCNP are depressed in PD, are likely to result from diminished reabsorption from central sources, and may be useful in monitoring onset and effects of therapeutic interventions in PD.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Creatinine; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Parkinson Disease; Peptide Fragments; Regression Analysis; Young Adult

C-type natriuretic peptide (CNP) is a neurotrophic factor widely expressed in the central nervous system including the basal ganglia, limbic system and hypothalamus. Nothing is known of CNP's role in the human brain but in rodents CNP promotes axon growth and branching, and interacts with dopaminergic function in models of addiction. Because preliminary evidence showed reduced levels in Parkinson's disease (PD), we examined concentrations of CNP peptides in cerebrospinal fluid (CSF) in 146 PD patients from the DATATOP study to determine changes over time in relation to medication status and cognitive function. CNP and an aminoterminal product of proCNP (NTproCNP) were measured in extracts from stored CSF by radioimmunoassay. CSF samples were obtained twice-at enrolment and at the study's endpoint (requirement for levodopa treatment) after treatment with placebo or deprenyl. At enrolment, median baseline concentration of CSF NTproCNP (776 pmol/L, n = 146) was significantly lower than that in a reference group without neurological disorder (1,010 pmol/L, p < 0.001). Concentrations declined significantly during placebo (p = 0.02) and lower values at enrolment were associated with more rapid functional decline (p < 0.01). In contrast, deprenyl-a treatment which delayed the need for levodopa-nullified the time-dependent decline in CSF NTproCNP. In conclusion subnormal CSF NTproCNP which declines with time and associates with increasing functional disability implicates CNP in PD. Concordant clinical and peptide responses to deprenyl suggest that some of the benefits of monoamine oxidase inhibitors in PD are mediated by preserving tissue CNP activity.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Cognition Disorders; Female; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type; Parkinson Disease; Retrospective Studies; Selegiline; Severity of Illness Index; Time Factors

There is rapidly growing evidence for the influence of inflammation on the development and progression of Parkinson's disease (PD). N-terminal pro C-type Natriuretic Peptide (NT-proCNP) is a novel potential inflammatory biomarker and has been recently correlated in PD with pro- and anti-inflammatory cytokines, especially TNF-α and IL-10. The study aims to explore serum level of NT-proCNP in group consisted of 132 patients with idiopathic Parkinson's disease (age 59.6±15.l years) and 46 healthy controls (age 58.5±11.5 years). Serum level of NT-proCNP was significantly higher in PD patients than in the control group (p<0.05; PD vs control: mean 3.65±5.5 vs 1.49±0.73, median 1.81 vs 1.46). The serum level of NT-proCNP was directly correlated with the treatment with dopamine agonist (ropinirole) (R=0.38; p<0.05). The higher serum level of NT-proCNP in PD patients being treated with ropinirole suggests a potential proinflammatory characteristic of dopamine agonists.

Topics: Adult; Antiparkinson Agents; Biomarkers; Case-Control Studies; Dopamine Agonists; Female; Humans; Indoles; Inflammation; Male; Middle Aged; Natriuretic Peptide, C-Type; Parkinson Disease

The role of inflammatory factors in Parkinson's disease (PD) has not been consistently proven yet. Despite the presence of some potentially causative factors, the primary and initiating factor has not been determined. Therefore the influence of proinflammatory and antiphlogistic factors on the risk of PD remains unclear. The aim of the study was to evaluate the level of NT-proCNP as well as proinflammatory factors in peripheral blood of patients with PD and to compare the changes of cytokines and NT-proCNP profile of these patients with the profile within the control group.. The study group consisted of 60 patients with the diagnosis of idiopathic PD, in the mean age of 59 ± 15.5 years, and control group of 24 persons, in the mean age of 64 ± 5.8 years, without neurodegenerative and inflammatory disorders. The quantitative determination of cytokines was evaluated with the fluorokine MAP cytokine multiplex kit and the Luminex 100 Platform. ELISA kits were used for the quantitative determination of human NT-proCNP.. The levels of NT-proCNP and all measured cytokines were higher in serum of PD patients in comparison to the control group, though the significant differences were only observed in relation to serum level of NT-proCNP (p<0.05) and TNF-α (p<0.001). The mean serum level of NT-proCNP in PD patients correlates with the level of TNF-α (R=0.359, p<0.05) and IL-10 (R=-0.39, p=0.05). There are also other correlations in serum of PD group: between IL-10 and IL-12 (R=0.39, p=0.05), IL-6 and IL-1ß (R=0.65, p=0.05). The serum level of IL-6 is also in a positive relation with H&Y stage (R=0.27, p=0.05).. The concentration of NT-proCNP and TNF-α is essentially higher in parkinsonian patients than in healthy group. The levels of other anti- and proinflammatory cytokines also tend to be higher in PD patients in comparison to the control group. It confirms the significance of these factors' influence on molecular pathogenesis of PD and makes NT-proCNP a new potential determinant of inflammation in PD patients.

Topics: Cytokines; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, C-Type; Parkinson Disease