Brain-derived neurotrophic factor (BDNF) signaling pathway (WP2380)

Homo sapiens

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, behavior, mental health, learning, memory, stress, pain and apoptosis. BDNF is implicated in various neuronal disorders such as Alzheimer's disease, Huntington's disease, depression, and bipolar disorder. BDNF binds to tyrosine kinase receptor known as tropomyosin-related kinase B (TrkB). It also binds with low affinity to p75 neurotrophin receptor (p75NTR). BDNF and its receptors are expressed throughout the central and peripheral nervous system. BDNF signaling is elicited when it dimerizes and binds to TrkB, resulting in the receptor dimerization and autophosphorylation. The activation of the receptor results in its interaction with molecules such as Shp2, Shc and PLC-gamma. These molecules further interact and modify their downstream targets leading to various neuronal processes. BDNF activates the signaling cascades such as PLC/PKC, PI3K/Akt, Ras/Erk, AMPK/ACC and NFκB pathways. BDNF through PLC/PKC pathway leads to release of intracellular calcium and regulation of synaptic plasticity. It also maintains synaptic plasticity through cAMP/PKA signaling. Activation of PI3K/Akt pathway through BDNF/TrkB interaction inhibits cell apoptosis by decreasing the expression of BIM. However, BDNF/p75NTR interaction activates JNK through TRAF6, which leads to apoptosis. Activation of JNK3 also leads to proteolytic cleavage of the p75NTR by TACE. PI3K/Akt also leads to activation of mTOR pathway and subsequently protein synthesis. Ras/Erk signaling is involved in cell proliferation, differentiation and protection of neurons. BDNF also leads to neuronal survival through Erk5/Mef pathway. Phosphorylation of synapsin by Erk1/2 leads to neurotransmitter release. BDNF signaling leads to nitric oxide production through NFκB pathway. BDNF induces neurite outgrowth through activation of JAK/STAT, Rac, and Cdc42 pathways. BDNF enhances oxidation of fat through AMPK mediated inhibition of ACC. It also plays role in microtubule assembly through inhibition of GSK3-beta. It leads to oxidative neuronal necrosis through activation of NCF molecules. BDNF also regulates the surface expression of AMPA and NMDA receptors. BDNF also regulates the expression of genes leading to processes such as differentiation of dendrites and calcification of cementoblast-like cells. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


NetPath , Christine Chichester , Egon Willighagen , Zahra Roudbari , Chris Evelo , Martina Summer-Kutmon , Kristina Hanspers , and Eric Weitz


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Homo sapiens



Pathway Ontology

brain-derived neurotrophic factor signaling pathway


Label Type Compact URI Comment
IP3 Metabolite hmdb:HMDB0001143
PIP2 Metabolite wikidata:Q3083814
DAG Metabolite chebi:18035
PIP2 Metabolite wikidata:Q3083814
PIP3 Metabolite chebi:16618
cAMP Metabolite chebi:17489
IKK2 GeneProduct ncbigene:3551
IkkG GeneProduct ncbigene:8517
IKK1 GeneProduct ncbigene:1147
CYFIP1 GeneProduct ncbigene:23191
VAV3 Protein ncbigene:10451
MAPK9 Protein ncbigene:5601
CDK5R1 Protein ncbigene:8851
SHC2 Protein ncbigene:25759
MAPK8 Protein ncbigene:5599
MAPK3 Protein ncbigene:5595
NCK1 Protein ncbigene:4690
NCK2 Protein ncbigene:8440
SHC1 Protein ncbigene:6464
PLCG1 Protein ncbigene:5335
PTPN11 Protein ncbigene:5781
CDH2 Protein ncbigene:1000
TRAF6 Protein ncbigene:7189
CTNNB1 Protein ncbigene:1499
SQSTM1 Protein ncbigene:8878
FYN Protein ncbigene:2534
SHC3 Protein ncbigene:53358
NGFR Protein ncbigene:4804
NCAM1 Protein ncbigene:4684
TIAM1 Protein ncbigene:7074
LINGO1 Protein ncbigene:84894
RANBP9 Protein ncbigene:10048
DOK5 Protein ncbigene:55816
SHC4 Protein ncbigene:399694
GRB2 Protein ncbigene:2885
SIRPA Protein ncbigene:140885
KCNA3 Protein ncbigene:3738
FRS2 Protein ncbigene:10818
GRIN2B Protein ncbigene:2904
FRS3 Protein ncbigene:10817
DOCK3 Protein ncbigene:1795
NTRK1 Protein ncbigene:4914
RAC1 Protein ncbigene:5879
CDKL5 Protein ncbigene:6792
SORT1 Protein ncbigene:6272
NGF Protein ncbigene:4803
BDNF Protein ncbigene:627
GRIA2 Protein ncbigene:2891
CREB1 Protein ncbigene:1385
NSF Protein ncbigene:4905
GNB2L1 Protein ncbigene:10399
GABRB3 Protein ncbigene:2562
PPP2CA Protein ncbigene:5515
CRTC1 Protein ncbigene:23373
KSR1 Protein ncbigene:8844
MAP2K2 Protein ncbigene:5605
MAPK1 Protein ncbigene:5594
MAP2K1 Protein ncbigene:5604
SH2B2 Protein ncbigene:10603
FOXO3 Protein ncbigene:2309
MTOR Protein ncbigene:2475
KIDINS220 Protein ncbigene:57498
RPS6KB1 Protein ncbigene:6198
EIF4EBP1 Protein ncbigene:1978
AKT1 Protein ncbigene:207
BAD Protein ncbigene:572
SH2B Protein ncbigene:25970
GSK3B Protein ncbigene:2932
GRIN1 Protein ncbigene:2902
IRS2 Protein ncbigene:8660
MAPK7 Protein ncbigene:5598
IRS1 Protein ncbigene:3667
TSC2 Protein ncbigene:7249
GRIA1 Protein ncbigene:2890
CAMK4 Protein ncbigene:814
CAMK2 Protein ncbigene:815
EEF2 Protein ncbigene:1938
ACACB Protein ncbigene:32
PRKAA2 Protein ncbigene:5563
MAPT Protein ncbigene:4137
ELK1 Protein ncbigene:2002
IGF2BP1 Protein ncbigene:10642
PTK2B Protein ncbigene:2185
RAF1 Protein ncbigene:5894
VAV2 Protein ncbigene:7410
CDK5 Protein ncbigene:1020
NFATC4 Protein ncbigene:4776
NCF2 Protein ncbigene:4688
NCF1 Protein ncbigene:653361
NFATC4 Protein ncbigene:4776
STAT5B Protein ncbigene:6777
CDC42 Protein ncbigene:998
CNR1 Protein ncbigene:1268
NTRK3 Protein ncbigene:4916
PIK3R1 Protein ncbigene:5295
NTF3 Protein ncbigene:4908
BDNF Protein ncbigene:627
PDPK1 Protein ncbigene:5170
MAP3K1 Protein ncbigene:4214
ADAM17 Protein ncbigene:6868
MAPK10 Protein ncbigene:5602
HRAS Protein ncbigene:3265
RPS6 Protein ncbigene:6194
EIF4E Protein ncbigene:1977
PIK3R2 Protein ncbigene:5296
SRC Protein ncbigene:6714
FOXO3 Protein ncbigene:2309
STAT5A Protein ncbigene:6776
NFKB1 Protein ncbigene:4790
RELA Protein ncbigene:5970
NFKB1 Protein ncbigene:4790
RELA Protein ncbigene:5970
NFKBIA Protein ncbigene:4792
JUN Protein ncbigene:3725
CASP3 Protein ncbigene:836
RPS6KA3 Protein ncbigene:6197
YBX1 Protein ncbigene:4904
RPS6KA1 Protein ncbigene:6195
RPS6KA5 Protein ncbigene:9252
CAMK1 Protein ncbigene:8536
MAPK14 Protein ncbigene:1432
RASGRF1 Protein ncbigene:5923
DPYSL2 Protein ncbigene:1808
APC Protein ncbigene:324
PTPRF Protein ncbigene:5792
DLG1 Protein ncbigene:1739
GRIP1 Protein ncbigene:23426
GRIA3 Protein ncbigene:2892
RHOG Protein ncbigene:391
KCNN2 Protein ncbigene:3781
CFL1 Protein ncbigene:1072
BDNF Protein ncbigene:627
BDNF Protein ncbigene:627
PIK3CA Protein ncbigene:5296
PRKAA1 Protein ncbigene:5562
MAP2K5 Protein ncbigene:5607
MAP3K2 Protein ncbigene:10746
MEF2C Protein ncbigene:4208
MEF2A Protein ncbigene:4205
RAP1A Protein ncbigene:5906
MAPK7 Protein ncbigene:5598
STAT5B Protein ncbigene:6777
STAT5A Protein ncbigene:6776
JAK2 Protein ncbigene:3717
STAT1 Protein ncbigene:6772
STAT3 Protein ncbigene:6774
CEBPB Protein ncbigene:1385
MARCKS Protein ncbigene:4082
PRKCD Protein ncbigene:5580
NTRK2 Protein ncbigene:4915
NTRK2 Protein ncbigene:4915
GSK3B Protein ncbigene:2932
CSNK2A1 Protein ncbigene:1457
RAB3A Protein ncbigene:5864
EIF2S1 Protein ncbigene:1965
EIF2S2 Protein ncbigene:8894
MAPK3 Protein ncbigene:5595
MAPK1 Protein ncbigene:5594
SYN1 Protein ncbigene:6853
RPS6KA5 Protein ncbigene:9252