Department of Neuroscience; Neurology, Uppsala University, Uppsala, Sweden.
Institute of Neuroscience and Physiology; Clinical Neuroscience, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Mov Disord. 2021 Feb;36(2):481-491. doi: 10.1002/mds.28391. Epub 2020 Nov 28.
Identifying molecular changes that contribute to the onset and progression of Huntington's disease (HD) is of importance for the development and evaluation of potential therapies.
We conducted an unbiased mass-spectrometry proteomic analysis on the cerebrospinal fluid of 12 manifest HD patients (ManHD), 13 pre-manifest (preHD), and 38 controls. A biologically plausible and significant possible biomarker was validated in samples from a separate cohort of patients and controls consisting of 23 ManHD patients and 23 controls.
In ManHD compared to preHD, 10 proteins were downregulated and 43 upregulated. Decreased levels of proenkephalin (PENK) and transthyretin were closely linked to HD symptom severity, whereas levels of 15 upregulated proteins were associated with symptom severity. The decreased PENK levels were replicated in the separate cohort where absolute quantitation was performed.
We hypothesize that declining PENK levels reflect the degeneration of medium spiny neurons (MSNs) that produce PENK and that assays for PENK may serve as a surrogate marker for the state of MSNs in HD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
鉴定导致亨廷顿病（HD）发病和进展的分子变化对于潜在治疗方法的开发和评估很重要。
我们对 12 名显性亨廷顿病（ManHD）患者、13 名前期（preHD）和 38 名对照组的脑脊液进行了无偏质谱蛋白质组学分析。在由 23 名 ManHD 患者和 23 名对照组组成的另一个队列的样本中，验证了一个具有生物学意义且显著的可能生物标志物。
与 preHD 相比，ManHD 中有 10 种蛋白下调，43 种蛋白上调。前脑啡肽（PENK）和转甲状腺素水平降低与 HD 症状严重程度密切相关，而 15 种上调蛋白的水平与症状严重程度相关。在进行绝对定量的另一个队列中，复制了 PENK 水平降低的现象。
我们假设 PENK 水平的下降反映了产生 PENK 的中型棘突神经元（MSNs）的退化，并且 PENK 测定可能作为 HD 中 MSNs 状态的替代标志物。 © 2020 作者。运动障碍由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。
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