C-type natriuretic peptide in Parkinson's disease: reduced secretion and response to deprenyl
C-type natriuretic peptide in Parkinson's disease: reduced secretion and response to deprenyl
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DOI：
10.1007/s00702-013-1123-9
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发表时间：
2014-04-01
影响因子：
3.3
通讯作者：
Anderson, T. J.
中科院分区：
文献类型：
--
作者：
Espiner, E. A.;Dalrymple-Alford, J. C.;Anderson, T. J.
C型利钠肽(CNP)是一种神经营养因子，广泛表达于中枢神经系统，包括基底节、边缘系统和下丘脑。CNP在人脑中的作用尚不清楚，但在啮齿类动物中，CNP促进轴突生长和分支，并在成瘾模型中与多巴胺能功能相互作用。由于初步证据显示帕金森氏病(PD)患者的水平降低，我们检测了DATATOP研究中146名PD患者脑脊液(CSF)中CNP多肽的浓度，以确定随时间的变化与药物状况和认知功能的关系。用放射免疫法测定脑脊液提取液中CNP及其氨基末端产物NTproCNP的含量。脑脊液样本被采集了两次--在登记时和研究结束时(左旋多巴治疗的要求)，在使用安慰剂或丙戊烯治疗后。在登记时，脑脊液NTproCNP基线浓度的中位数(776pmoL/L，n=146)显著低于无神经功能障碍的参照组(1010pmoL/L，p<；0.001)。在服用安慰剂期间，血药浓度显著下降(p=0.02)，登记时较低的血药浓度与更快的功能下降有关(p<；0.01)。相反，丙戊烯--一种推迟需要左旋多巴的治疗--抵消了脑脊液NTproCNP随时间的下降。综上所述，脑脊液NTproCNP低于正常水平，随着时间的推移而下降，并伴随着功能障碍的增加，与CNP在PD中有关。对异丙肾上腺素的一致临床反应和多肽反应表明，单胺氧化酶抑制剂在帕金森病中的一些益处是通过保留组织CNP活性来实现的。
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.