C-type natriuretic peptide in Parkinson’s disease: reduced secretion and response to deprenyl
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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.
KeywordsParkinson’s disease CSF NTproCNP Monoamine oxidase inhibitors
This work was supported by a grant from the Michael J Fox Foundation for Parkinson’s Research. Samples from the DATATOP study conducted by the Parkinson Study Group and sent from the DNA and Cell Laboratory at Indiana University with support from The Michael J Fox Foundation, were used in this study. We thank contributors, including all members of the Parkinson Study Group who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. Special thanks are due to Peggy Auinger, University of Rochester Medical Center, for her assistance in selecting appropriate samples for assay.
Conflict of interest
The Authors have nothing to declare.
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