Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

All data generated or analysed during this study are included in this published article and its supplementary information files.

References

  1. Bellani S, Sousa VL, Ronzitti G, Valtorta F, Meldolesi J, Chieregatti E (2010) The regulation of synaptic function by α-synuclein. Commun Integr Biol 3(2):106–109. https://doi.org/10.4161/cib.3.2.10964

    Article  PubMed  PubMed Central  Google Scholar 

  2. Emamzadeh FN (2016) α-synuclein structure, functions, and interactions. J Res Med Sci 21:29. https://doi.org/10.4103/1735-1995.181989

    Article  PubMed  PubMed Central  Google Scholar 

  3. Goedert M, Jakes R, Spillantini MG (2017) The synucleinopathies: twenty years on. J Parkinsons Dis 7(s1):S51–S69. https://doi.org/10.3233/JPD-179005

    Article  PubMed  PubMed Central  Google Scholar 

  4. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies. Proc Natl Acad Sci U S A 95(11):6469–6473. https://doi.org/10.1073/pnas.95.11.6469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jellinger KA, Lantos PL (2010) Papp-Lantos inclusions and the pathogenesis of multiple system atrophy: an update. Acta Neuropathol 119(6):657–667. https://doi.org/10.1007/s00401-010-0672-3

    Article  CAS  PubMed  Google Scholar 

  6. Braak H, Sastre M, Del Tredici K (2007) Development of α-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 114(3):231–241. https://doi.org/10.1007/s00401-007-0244-3

    Article  CAS  PubMed  Google Scholar 

  7. Wakabayashi K, Hayashi S, Yoshimoto M, Kudo H, Takahashi H (2000) NACP/α-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains. Acta Neuropathol 99(1):14–20. https://doi.org/10.1007/pl00007400

    Article  CAS  PubMed  Google Scholar 

  8. Song YJ, Halliday GM, Holton JL, Lashley T, O’Sullivan SS, McCann H, Lees AJ, Ozawa T et al (2009) Degeneration in different parkinsonian syndromes relates to astrocyte type and astrocyte protein expression. J Neuropathol Exp Neurol 68(10):1073–1083. https://doi.org/10.1097/NEN.0b013e3181b66f1b

    Article  CAS  PubMed  Google Scholar 

  9. Sorrentino ZA, Giasson BI, Chakrabarty P (2019) α-Synuclein and astrocytes: tracing the pathways from homeostasis to neurodegeneration in Lewy body disease. Acta Neuropathol 138(1):1–21. https://doi.org/10.1007/s00401-019-01977-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Booth HDE, Hirst WD, Wade-Martins R (2017) The role of astrocyte dysfunction in Parkinson’s disease pathogenesis. Trends Neurosci 40(6):358–370. https://doi.org/10.1016/j.tins.2017.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Verkhratsky A, Nedergaard M (2018) Physiology of astroglia. Physiol Rev 98(1):239–389. https://doi.org/10.1152/physrev.00042.2016

    Article  CAS  PubMed  Google Scholar 

  12. Verkhratsky A, Zorec R, Parpura V (2017) Stratification of astrocytes in healthy and diseased brain. Brain Pathol 27(5):629–644. https://doi.org/10.1111/bpa.12537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kosel S, Egensperger R, von Eitzen U, Mehraein P, Graeber MB (1997) On the question of apoptosis in the parkinsonian substantia nigra. Acta Neuropathol 93(2):105–108. https://doi.org/10.1007/s004010050590

    Article  CAS  PubMed  Google Scholar 

  14. Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H (2010) Astrocytic expression of Parkinson’s disease-related A53T α-synuclein causes neurodegeneration in mice. Mol Brain 3:12. https://doi.org/10.1186/1756-6606-3-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Verkhratsky A, Matteoli M, Parpura V, Mothet JP, Zorec R (2016) Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion. EMBO J 35(3):239–257. https://doi.org/10.15252/embj.201592705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cabezas R, Avila-Rodriguez M, Vega-Vela NE, Echeverria V, Gonzalez J, Hidalgo OA, Santos AB, Aliev G et al (2016) Growth Factors and astrocytes metabolism: possible roles for platelet derived growth factor. Med Chem 12(3):204–210. https://doi.org/10.2174/1573406411666151019120444

    Article  CAS  PubMed  Google Scholar 

  17. Mattson MP (2008) Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci 1144:97–112. https://doi.org/10.1196/annals.1418.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Peterson AL, Nutt JG (2008) Treatment of Parkinson’s disease with trophic factors. Neurotherapeutics 5(2):270–280. https://doi.org/10.1016/j.nurt.2008.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Stepanenko AA, Heng HH (2017) Transient and stable vector transfection: pitfalls, off-target effects, artifacts. Mutat Res 773:91–103. https://doi.org/10.1016/j.mrrev.2017.05.002

    Article  CAS  Google Scholar 

  20. Gezen-Ak D, Atasoy IL, Candas E, Alaylioglu M, Yilmazer S, Dursun E (2017) Vitamin D receptor regulates amyloid β1-42 production with protein disulfide isomerase A3. ACS Chem Neurosci 8(10):2335–2346. https://doi.org/10.1021/acschemneuro.7b00245

    Article  CAS  PubMed  Google Scholar 

  21. Atasoy IL, Dursun E, Gezen-Ak D, Metin-Armagan D, Ozturk M, Yilmazer S (2017) Both secreted and the cellular levels of BDNF attenuated due to tau hyperphosphorylation in primary cultures of cortical neurons. J Chem Neuroanat 80:19–26. https://doi.org/10.1016/j.jchemneu.2016.11.007

    Article  CAS  PubMed  Google Scholar 

  22. Dursun E, Gezen-Ak D, Yilmazer S (2014) The influence of vitamin D treatment on the inducible nitric oxide synthase (INOS) expression in primary hippocampal neurons. Noro Psikiyatr Ars 51(2):163–168. https://doi.org/10.4274/npa.y7089

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gezen-Ak D, Dursun E, Yilmazer S (2014) The effect of vitamin D treatment on nerve growth factor (NGF) release from hippocampal neurons. Noro Psikiyatr Ars 51(2):157–162. https://doi.org/10.4274/npa.y7076

    Article  PubMed  PubMed Central  Google Scholar 

  24. Dursun E, Candas E, Yilmazer S, Gezen-Ak D (2019) Amyloid β1-42 Alters the expression of miRNAs in cortical neurons. J Mol Neurosci 67(2):181–192. https://doi.org/10.1007/s12031-018-1223-y

    Article  CAS  PubMed  Google Scholar 

  25. Dursun E, Gezen-Ak D (2017) Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin. PLoS One 12(11):e0188605. https://doi.org/10.1371/journal.pone.0188605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, Haw R, Jassal B et al (2018) The reactome pathway knowledgebase. Nucleic Acids Res 46(D1):D649–D655. https://doi.org/10.1093/nar/gkx1132

    Article  CAS  PubMed  Google Scholar 

  27. Jassal B, Matthews L, Viteri G, Gong C, Lorente P, Fabregat A, Sidiropoulos K, Cook J et al (2020) The reactome pathway knowledgebase. Nucleic Acids Res 48(D1):D498–D503. https://doi.org/10.1093/nar/gkz1031

    Article  CAS  PubMed  Google Scholar 

  28. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT et al (2019) STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607–D613. https://doi.org/10.1093/nar/gky1131

    Article  CAS  PubMed  Google Scholar 

  29. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. https://doi.org/10.1101/gr.1239303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ramaswamy S, Kordower JH (2009) Are growth factors the answer? Parkinsonism Relat Disord 15(Suppl 3):S176–S180. https://doi.org/10.1016/S1353-8020(09)70809-0

    Article  PubMed  Google Scholar 

  31. Yasuda T, Mochizuki H (2010) Use of growth factors for the treatment of Parkinson’s disease. Expert Rev Neurother 10(6):915–924. https://doi.org/10.1586/ern.10.55

    Article  CAS  PubMed  Google Scholar 

  32. Pennuto M, Pandey UB, Polanco MJ (2020) Insulin-like growth factor 1 signaling in motor neuron and polyglutamine diseases: from molecular pathogenesis to therapeutic perspectives. Front Neuroendocrinol:100821. https://doi.org/10.1016/j.yfrne.2020.100821

  33. Weis J, Saxena S, Evangelopoulos ME, Kruttgen A (2003) Trophic factors in neurodegenerative disorders. IUBMB Life 55(6):353–357. https://doi.org/10.1080/1521654031000153021

    Article  CAS  PubMed  Google Scholar 

  34. Sonntag WE, Ramsey M, Carter CS (2005) Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging. Ageing Res Rev 4(2):195–212. https://doi.org/10.1016/j.arr.2005.02.001

    Article  CAS  PubMed  Google Scholar 

  35. Logan S, Pharaoh GA, Marlin MC, Masser DR, Matsuzaki S, Wronowski B, Yeganeh A, Parks EE et al (2018) Insulin-like growth factor receptor signaling regulates working memory, mitochondrial metabolism, and amyloid-beta uptake in astrocytes. Mol Metab 9:141–155. https://doi.org/10.1016/j.molmet.2018.01.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Suzuki K, Ikegaya Y, Matsuura S, Kanai Y, Endou H, Matsuki N (2001) Transient upregulation of the glial glutamate transporter GLAST in response to fibroblast growth factor, insulin-like growth factor and epidermal growth factor in cultured astrocytes. J Cell Sci 114(Pt 20):3717–3725

    CAS  PubMed  Google Scholar 

  37. Genis L, Davila D, Fernandez S, Pozo-Rodrigalvarez A, Martinez-Murillo R, Torres-Aleman I (2014) Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury. F1000Res 3:28. https://doi.org/10.12688/f1000research.3-28.v2

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ni W, Rajkumar K, Nagy JI, Murphy LJ (1997) Impaired brain development and reduced astrocyte response to injury in transgenic mice expressing IGF binding protein-1. Brain Res 769(1):97–107. https://doi.org/10.1016/s0006-8993(97)00676-8

    Article  CAS  PubMed  Google Scholar 

  39. Aberg ND, Brywe KG, Isgaard J (2006) Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain. ScientificWorldJournal 6:53–80. https://doi.org/10.1100/tsw.2006.22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ratcliffe LE, Vazquez Villasenor I, Jennings L, Heath PR, Mortiboys H, Schwartzentruber A, Karyka E, Simpson JE et al (2018) Loss of IGF1R in human astrocytes alters complex I activity and support for neurons. Neuroscience 390:46–59. https://doi.org/10.1016/j.neuroscience.2018.07.029

    Article  CAS  PubMed  Google Scholar 

  41. Funa K, Sasahara M (2014) The roles of PDGF in development and during neurogenesis in the normal and diseased nervous system. J NeuroImmune Pharmacol 9(2):168–181. https://doi.org/10.1007/s11481-013-9479-z

    Article  PubMed  Google Scholar 

  42. Ballagi AE, Odin P, Othberg-Cederstrom A, Smits A, Duan WM, Lindvall O, Funa K (1994) Platelet-derived growth factor receptor expression after neural grafting in a rat model of Parkinson’s disease. Cell Transplant 3(6):453–460. https://doi.org/10.1177/096368979400300602

    Article  CAS  PubMed  Google Scholar 

  43. Iihara K, Hashimoto N, Tsukahara T, Sakata M, Yanamoto H, Taniguchi T (1997) Platelet-derived growth factor-BB, but not -AA, prevents delayed neuronal death after forebrain ischemia in rats. J Cereb Blood Flow Metab 17(10):1097–1106. https://doi.org/10.1097/00004647-199710000-00012

    Article  CAS  PubMed  Google Scholar 

  44. Funa K, Ahgren A (1997) Characterization of platelet-derived growth factor (PDGF) action on a mouse neuroblastoma cell line, NB41, by introduction of an antisense PDGF beta-receptor RNA. Cell Growth Differ 8(8):861–869

    CAS  PubMed  Google Scholar 

  45. Zhang SX, Gozal D, Sachleben LR Jr, Rane M, Klein JB, Gozal E (2003) Hypoxia induces an autocrine-paracrine survival pathway via platelet-derived growth factor (PDGF)-B/PDGF-beta receptor/phosphatidylinositol 3-kinase/Akt signaling in RN46A neuronal cells. FASEB J 17(12):1709–1711. https://doi.org/10.1096/fj.02-1111fje

    Article  CAS  PubMed  Google Scholar 

  46. Lim R, Liu YX, Zaheer A (1990) Cell-surface expression of glia maturation factor beta in astrocytes. FASEB J 4(15):3360–3363. https://doi.org/10.1096/fasebj.4.15.2253851

    Article  CAS  PubMed  Google Scholar 

  47. Zaheer A, Mathur SN, Lim R (2002) Overexpression of glia maturation factor in astrocytes leads to immune activation of microglia through secretion of granulocyte-macrophage-colony stimulating factor. Biochem Biophys Res Commun 294(2):238–244. https://doi.org/10.1016/S0006-291X(02)00467-9

    Article  CAS  PubMed  Google Scholar 

  48. Kempuraj D, Khan MM, Thangavel R, Xiong Z, Yang E, Zaheer A (2013) Glia maturation factor induces interleukin-33 release from astrocytes: implications for neurodegenerative diseases. J NeuroImmune Pharmacol 8(3):643–650. https://doi.org/10.1007/s11481-013-9439-7

    Article  PubMed  PubMed Central  Google Scholar 

  49. Krum JM, Khaibullina A (2003) Inhibition of endogenous VEGF impedes revascularization and astroglial proliferation: roles for VEGF in brain repair. Exp Neurol 181(2):241–257. https://doi.org/10.1016/s0014-4886(03)00039-6

    Article  CAS  PubMed  Google Scholar 

  50. Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13(2):89–102. https://doi.org/10.1038/nrm3270

    Article  CAS  PubMed  Google Scholar 

  51. Martin-Jimenez CA, Garcia-Vega A, Cabezas R, Aliev G, Echeverria V, Gonzalez J, Barreto GE (2017) Astrocytes and endoplasmic reticulum stress: a bridge between obesity and neurodegenerative diseases. Prog Neurobiol 158:45–68. https://doi.org/10.1016/j.pneurobio.2017.08.001

    Article  CAS  PubMed  Google Scholar 

  52. Thayanidhi N, Helm JR, Nycz DC, Bentley M, Liang Y, Hay JC (2010) Alpha-synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol Biol Cell 21(11):1850–1863. https://doi.org/10.1091/mbc.E09-09-0801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lai Y, Kim S, Varkey J, Lou X, Song JK, Diao J, Langen R, Shin YK (2014) Nonaggregated α-synuclein influences SNARE-dependent vesicle docking via membrane binding. Biochemistry 53(24):3889–3896. https://doi.org/10.1021/bi5002536

    Article  CAS  PubMed  Google Scholar 

  54. Colla E, Coune P, Liu Y, Pletnikova O, Troncoso JC, Iwatsubo T, Schneider BL, Lee MK (2012) Endoplasmic reticulum stress is important for the manifestations of α-synucleinopathy in vivo. J Neurosci 32(10):3306–3320. https://doi.org/10.1523/JNEUROSCI.5367-11.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Alberdi E, Wyssenbach A, Alberdi M, Sanchez-Gomez MV, Cavaliere F, Rodriguez JJ, Verkhratsky A, Matute C (2013) Ca2+-dependent endoplasmic reticulum stress correlates with astrogliosis in oligomeric amyloid β-treated astrocytes and in a model of Alzheimer’s disease. Aging Cell 12(2):292–302. https://doi.org/10.1111/acel.12054

    Article  CAS  PubMed  Google Scholar 

  56. Matsuzaki H, Daitoku H, Hatta M, Tanaka K, Fukamizu A (2003) Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proc Natl Acad Sci U S A 100(20):11285–11290. https://doi.org/10.1073/pnas.1934283100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Vlachostergios PJ, Papandreou CN (2013) The Bmi-1/NF-kappaB/VEGF story: another hint for proteasome involvement in glioma angiogenesis? J Cell Commun Signal 7(4):235–237. https://doi.org/10.1007/s12079-013-0198-2

    Article  PubMed  PubMed Central  Google Scholar 

  58. Chang J, Yang B, Zhou Y, Yin C, Liu T, Qian H, Xing G, Wang S et al (2019) Acute methylmercury exposure and the hypoxia-inducible factor-1α signaling pathway under normoxic conditions in the rat brain and astrocytes in vitro. Environ Health Perspect 127(12):127006. https://doi.org/10.1289/EHP5139

    Article  PubMed  PubMed Central  Google Scholar 

  59. Latina V, Caioli S, Zona C, Ciotti MT, Borreca A, Calissano P, Amadoro G (2018) NGF-dependent changes in ubiquitin homeostasis trigger early cholinergic degeneration in cellular and animal AD-model. Front Cell Neurosci 12:487. https://doi.org/10.3389/fncel.2018.00487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Du Y, Zhang X, Tao Q, Chen S, Le W (2013) Adeno-associated virus type 2 vector-mediated glial cell line-derived neurotrophic factor gene transfer induces neuroprotection and neuroregeneration in a ubiquitin-proteasome system impairment animal model of Parkinson’s disease. Neurodegener Dis 11(3):113–128. https://doi.org/10.1159/000334527

    Article  CAS  PubMed  Google Scholar 

  61. Nagano K, Bornhauser BC, Warnasuriya G, Entwistle A, Cramer R, Lindholm D, Naaby-Hansen S (2006) PDGF regulates the actin cytoskeleton through hnRNP-K-mediated activation of the ubiquitin E3-ligase MIR. EMBO J 25(9):1871–1882. https://doi.org/10.1038/sj.emboj.7601059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Papaevgeniou N, Chondrogianni N (2014) The ubiquitin proteasome system in Caenorhabditis elegans and its regulation. Redox Biol 2:333–347. https://doi.org/10.1016/j.redox.2014.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ebrahimi-Fakhari D, Cantuti-Castelvetri I, Fan Z, Rockenstein E, Masliah E, Hyman BT, McLean PJ, Unni VK (2011) Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of alpha-synuclein. J Neurosci 31(41):14508–14520. https://doi.org/10.1523/JNEUROSCI.1560-11.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The study is supported by the Scientific and Technological Research Council of Turkey-TUBITAK (Project No. 216S887) and by Research Fund of Istanbul University-Cerrahpasa (Project No: YKL-23616). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Brain and Neurodegenerative Disorders Research Laboratories, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Büşra Şengül, Erdinç Dursun & Duygu Gezen-Ak

  2. Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Erdinç Dursun

  3. Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

    Alexei Verkhratsky

  4. Achucarro Centre for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    Alexei Verkhratsky

Authors
  1. Büşra Şengül
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erdinç Dursun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexei Verkhratsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Duygu Gezen-Ak
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualisation: BS, DGA; data curation: BS; formal analysis: BS, ED, DGA; funding acquisition: DGA; investigation: BS, DGA; methodology: BS, ED, DGA; project administration: ED, DGA; resources: ED, DGA; supervision: AV, DGA; writing–original draft preparation: BS, ED, AV, DGA; writing–review and editing: AV, ED, DGA. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Alexei Verkhratsky or Duygu Gezen-Ak.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interests

Ethics Approval

Not applicable

Consent to Participate

Not applicable

Consent for Publication

Not applicable

Code Availability

Not applicable

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Supplementary figure 1:

Growth factor expression profile of human astrocytes. The 95% CI values of intracellular or secreted GF/GF receptors levels in untreated human astrocytes were set as upper or lower threshold values for GF production. For the calculation of 95% CI, mean levels of GFs at 48 hours and 72 hours were used (DOCX 14 kb)

Supplementary figure 2:

Growth factor expression profile of mock or α-synuclein overexpressing human astrocytes. The 95% CI values of intracellular or secreted GF/GF receptors levels in each group were set as upper or lower threshold values for GF detection. For the calculation of 95% CI, mean levels of GFs at 48 hours (the most significant time point). (DOCX 18 kb)

Supplementary table 1:

Reactome analysis results. Secreted or intracellular levels of 33 GFs and 8 GF receptors in control or α-synuclein overexpressing human astrocytes were used for analysis. Only the pathway results of secreted proteins in untreated human astrocytes were given. (https://reactome.org/PathwayBrowser/#/ANALYSIS=MjAyMDAyMjcwOTQyMzNfMzQyMzU%3D) (DOCX 142 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Şengül, B., Dursun, E., Verkhratsky, A. et al. Overexpression of α-Synuclein Reorganises Growth Factor Profile of Human Astrocytes. Mol Neurobiol 58, 184–203 (2021). https://doi.org/10.1007/s12035-020-02114-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-020-02114-x

Keywords

Search

Navigation