Misfolding and accumulation of aberrant α-synuclein in the brain is associated with the distinct class of neurodegenerative diseases known as α-synucleinopathies, which include Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy. Pathological changes in astrocytes contribute to all neurological disorders, and astrocytes are reported to possess α-synuclein inclusions in the context of α-synucleinopathies. Astrocytes are known to express and secrete numerous growth factors, which are fundamental for neuroprotection, synaptic connectivity and brain metabolism; changes in growth factor secretion may contribute to pathobiology of neurological disorders. Here we analysed the effect of α-synuclein overexpression in cultured human astrocytes on growth factor expression and release. For this purpose, the intracellular and secreted levels of 33 growth factors (GFs) and 8 growth factor receptors (GFRs) were analysed in cultured human astrocytes by chemiluminescence-based western/dot blot. Overexpression of human α-synuclein in cultured foetal human astrocytes significantly changes the profile of GF production and secretion. We found that human astrocytes express and secrete FGF2, FGF6, EGF, IGF1, AREG, IGFBP2, IGFBP4, VEGFD, PDGFs, KITLG, PGF, TGFB3 and NTF4. Overexpression of human α-synuclein significantly modified the profile of GF production and secretion, with particularly strong changes in EGF, PDGF, VEGF and their receptors as well as in IGF-related proteins. Bioinformatics analysis revealed possible interactions between α-synuclein and EGFR and GDNF, as well as with three GF receptors, EGFR, CSF1R and PDGFRB.

大脑中异常 α-突触核蛋白的错误折叠和积累与称为 α-突触核蛋白病的不同类型的神经退行性疾病有关，其中包括帕金森病、路易体痴呆和多系统萎缩。星形胶质细胞的病理变化会导致所有神经系统疾病，据报道星形胶质细胞在 α-突触核蛋白病的背景下具有 α-突触核蛋白内含物。众所周知，星形胶质细胞可以表达和分泌多种生长因子，这些因子对于神经保护、突触连接和大脑代谢至关重要。生长因子分泌的变化可能有助于神经系统疾病的病理学。在这里，我们分析了 α-突触核蛋白在培养的人星形胶质细胞中过表达对生长因子表达和释放的影响。以此目的，通过基于化学发光的蛋白质印迹/斑点印迹分析培养的人星形胶质细胞中 33 种生长因子 (GF) 和 8 种生长因子受体 (GFR) 的细胞内和分泌水平。人 α-突触核蛋白在培养的胎儿人星形胶质细胞中的过表达显着改变了 GF 产生和分泌的特征。我们发现人星形胶质细胞表达和分泌 FGF2、FGF6、EGF、IGF1、AREG、IGFBP2、IGFBP4、VEGFD、PDGFs、KITLG、PGF、TGFB3 和 NTF4。人α-突触核蛋白的过度表达显着改变了GF产生和分泌的特征，尤其是EGF、PDGF、VEGF及其受体以及IGF相关蛋白的变化。生物信息学分析揭示了 α-突触核蛋白与 EGFR 和 GDNF 以及三种 GF 受体（EGFR、CSF1R 和 PDGFRB）之间可能存在相互作用。