华中科技大学曹学兵等研究人员合作发现，α-突触核蛋白纤维抑制BDNF/ERK信号通路在mPFC的激活，进而诱导类帕金森病的变化并伴有抑郁症状。相关论文于2024年11月28日在线发表在《神经科学通报》杂志上。

研究人员表示，抑郁症（Dep）是帕金森病（PD）最常见的伴随症状之一，但关于PD-Dep发生的详细病理证据仍然不足。目前，使用常规药物干预治疗这两种疾病的症状仍然是一项艰巨的任务。

研究人员发现PD-Dep大鼠的内侧前额叶皮层（mPFC）中，细胞外信号调节激酶（ERK）的激活受损，转录和翻译水平降低，脑源性神经营养因子（BDNF）表达减少。

研究人员证明了α-突触核蛋白（pS129）的异常磷酸化诱导了型B的转谷氨酰胺激酶受体（TrkB）在神经元细胞膜上的滞留，从而导致BDNF/TrkB信号通路功能失调。

研究人员选择SEW2871作为改善剂，以上调ERK磷酸化。结果表明，PD-Dep大鼠在帕金森病和抑郁症状的行为表现上有所改善。此外，pS129的减少伴随着BDNF/ERK信号通路在PD-Dep大鼠mPFC中的功能恢复。

附：英文原文

Title: Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression

Author: Ma, Zhuoran, Xu, Yan, Lian, Piaopiao, Wu, Yi, Liu, Ke, Zhang, Zhaoyuan, Tang, Zhicheng, Yang, Xiaoman, Cao, Xuebing

Issue&Volume: 2024-11-28

Abstract: Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.

DOI: 10.1007/s12264-024-01323-x

Source: https://link.springer.com/article/10.1007/s12264-024-01323-x