Intracellular Neuroprotective Mechanisms in Neuron-Glial Networks Mediated by Glial Cell Line-Derived Neurotrophic Factor

Figure 8

Glial cell line-derived neurotrophic factor signalling pathways. GDNF binds to the GFRα/Ret-receptor complex and activates phosphoinositide-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Akt: protein kinase В; BAD: proapoptotic protein; c-fos: protein-regulator of transcription of a number of inducible genes; c-myc: gene, encoding protein-transcription factor; CREB: cAMP-dependent transcription factor; GDNF: glial cell line-derived neurotrophic factor; GFRα: specific coreceptor for GDNF; Grb2: adaptor protein; FLT3: receptor-type tyrosine-protein kinase FLT3; Jak: Janus kinase, intracellular, nonreceptor tyrosine kinase; m-TOR: protein kinase with serine-threonine specificity; MAPК: mitogen-activated protein kinase; МЕК: kinase of MAPK; NFκB: transcription nuclear factor kappa В; p53: transcription factor regulating the cellular cycle; PDK1: phosphoinositide independent protein kinase; PI3K: phosphoinositol-3-kinase; Raf: serine-threonine protein kinase; Ras: small GTF-binding protein; Ret: receptor with tyrosine kinase activity; SOS: guanine nucleotides exchange factor; STAT: signal transducer and activator of transcription proteins; VEGF: vascular endothelial growth factor.