Overexpression of α-Synuclein Reorganises Growth Factor Profile of Human Astrocytes

• Published in: Molecular neurobiology Vol. 58; no. 1; pp. 184 - 203
• Main Authors: Şengül, Büşra, Dursun, Erdinç, Verkhratsky, Alexei, Gezen-Ak, Duygu
• Format: Journal Article
• Language: English
• Published: New York Springer US 2021; Springer Nature B.V
• Subjects: Astrocytes; Atrophy; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chemiluminescence; Dementia disorders; Epidermal growth factor receptors; Fibroblast growth factor 2; Fibroblast growth factor 6; Glial cell line-derived neurotrophic factor; Growth factor receptors; Growth factors; Insulin-like growth factor I; Insulin-like growth factor-binding protein 2; Insulin-like growth factor-binding protein 4; Lewy bodies; Movement disorders; Neural networks; Neurobiology; Neurodegenerative diseases; Neurological disorders; Neurology; Neurosciences; Original Article; Parkinson's disease; Secretion; Synuclein; Vascular endothelial growth factor; α-Synuclein; Raf/MAPK pathway; Human astrocyte; PI3/Akt pathway; Growth factor receptors; Neurotrophic factors; Growth factors; α-Synucleinopathies
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-020-02114-x

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.