摘要
Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.
摘要译文
骨蛋白（PENK）和Prodynorphin（PDYN）是内源性阿片类肽，主要在纹状体中产生，并且在较小程度上是在大脑皮层中。在几种神经退行性疾病中，已经描述了pENK和PDYN的代谢失调和脑脊液（CSF）水平的变化。然而，迄今为止，尚无研究研究这些肽在零星克鲁兹菲尔特– jakob病（SCJD）的CSF中。使用液相色谱 - 形成反应监测质谱法，我们评估了25个对照中的CSF PDYN和PENK衍生的肽水平，而63例SCJD患者属于最普遍的分子亚型（MM（V）1，VV2和MV2K）。与对照组相比，每种SCJD亚型的penk衍生肽之一显着降低。相反，与SCJD MM（v）1和VV2亚型相比，SCJD MV2K的CSF选择性降低了PDYN衍生的肽，SCJD MV2K的CSF是一种更广泛的总体病理学的亚型，我们通过对皮质和纹状体神经元损失的半特质分析证实和星形细胞增多症。在SCJD CSF中，PENK和PDYN与神经退行性的CSF生物标志物有关，但与临床变量无关，并且诊断性能差。 CSF PDYN和PENK衍生的肽在SCJD中没有明显的诊断和预后值。但是，分子亚型之间的不同标记水平可能有助于更好地理解通过发散神经元靶向确定的表型异质性的基础。
Samir Abu-Rumeileh;Peggy Barschke;Patrick Oeckl;Simone Baiardi;Angela Mammana;Andrea Mastrangelo;Mhd Rami Al Shweiki;Petra Steinacker;Anna Ladogana;Sabina Capellari;Markus Otto;Piero Parchi. Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease[J]. International Journal of Molecular Sciences, 2022,23(4): 2051