Figure 1.

The modulation of neurotransmitters on common molecular pathways. Neurotransmitters mediate the transformation of extracellular ligand signaling into intracellular signaling through multiple kinds of receptors, thus, affecting cell proliferation, migration, metabolism, apoptosis, autophagy, survival, differentiation and angiogenesis. The main intracellular signaling includes RTK pathways, GPCR pathways, apoptosis and autophagy signaling pathways. The activation of RTKs and GPCRs are associated with Ca²⁺ flux, which has been considered as the initial impulse and critical modulator of GBM signaling. All neurotransmitters can be identified by GPCRs, while ACh, Glu, GABA and ATP secretion activate Ca²⁺ flux via ionotropic receptors. GPCR mainly consists of three families: (i) Gaq/11 family (including M1/3/5 mAChR, mGluR I, 5−HTR2, P2Y and Y1/2), (ii) Gi/o family (including M2/4 mAChR, mGluR II/III, GABABR, D2−4, P1 and 5−HTR1/5) and (iii) Gs family (including D1/5, NK−1R, 5−HTR4/6/7, β−AR and P1). The mTOR pathway plays a vital role in autophagy induction. NF−kB has been shown to get involved in tumorigenesis, tumor growth and tumor response to drugs as a transcription factor. Apoptosis is mainly related to two mechanisms: (i) the extrinsic pathways initiated by pro-apoptotic ligands and (ii) the intrinsic pathways mediated by mitochondrial permeabilization. Neurotransmitters become involved in the activation of pro−caspase−8/9/10/3.