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FLASH GENE
Symbol BDNF contributors: mct/pgu/shn - updated : 14-07-2016
HGNC name brain-derived neurotrophic factor
HGNC id 1033
DNA
TYPE functioning gene
STRUCTURE 67.16 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   transcription factor   HRE
text structure
  • nine functional promoters that are used tissue and brain-region specifically
  • promoters I, II, III, and IV (BDNF-PI, -PII, -PIII, and -PIV), BDNF-PI was markedly activated, as well as BDNF-PIII, by Ca(2+) signals evoked via neuronal activity
  • BDNF-RE-1 is located around 100 bp upstream of BDNF exon II
  • cis-elements and transcription factors regulating neuronal activity-dependent transcription of BDNF gene
  • MAPPING cloned Y linked N status confirmed
    Map pter - D11S1750 - D11S4152 - BDNF - D11S1324 - D11S4201 - cen
    Authors USCSC (2009)
    RNA
    TRANSCRIPTS type messenger
    text variants 1, 2, 4, 5, and 7-16 encode the same isoform (a)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 4755 - 247 - 1991 1889807
  • also called variant 1/isoform a or IX
  • the longest transcript
  • 2 - 4125 - 247 - 1991 1889807
  • also called variant 2/isoform a or IIc, BDNF2C, or 2-5
  • an additional segment in the 5'UTR
  • 2 - 4338 - 255 - 1991 1889807
  • also called variant 3/isoform b or I, BDNF1, or 1-5
  • an additional segment in the 5'UTR and in the coding region
  • 2 - 4016 - 247 - 1991 1889807
  • also called variant 4/isoform a or VIb or BDNF5
  • an additional segment in the 5'UTR
  • 2 - 4028 - 247 - 1991 1889807
  • also called variant 5/isoform a or IV, BDNF4, or 3-5
  • an additional segment in the 5'UTR
  • 2 - 3976 - 262 - 1991 1889807
  • also called variant 6/isoform c or VIIb, BDNF6B, or 4I-5
  • an additional segment in the 5'UTR and in the coding region
  • 2 - 3827 - 247 - 1991 1889807
    also called variant 7/isoform a or IIa or BDNF2A
    2 - 4042 - 247 - 1991 1889807
    also called variant 8/isoform a or BDNF2B
    2 - 3928 - 247 - 1991 1889807
    also called variant 9/isoform a or BDNF3
    2 - 3764 - 247 - 1991 1889807
    also called variant 10/isoform a or Va
    2 - 3774 - 276 - 1991 1889807
    also called variant 17/isoform d or Vb
    3 - 4057 - 329 - 1991 1889807
    also called variant 18/isoform e or V-VIII
    4 - 4174 - 247 - 1991 1889807
    also called variant 11/isoform a or V-VIII-VIIIh
    2 - 3916 - 247 - 1991 1889807
    aso called variant 12/isoform a or Vh
    2 - 3998 - 247 - 1991 1889807
    also called variant 13/isoform a or VIa
    3 - 4123 - 247 - 1991 1889807
    also called variant 14/isoform a or VIb-IXbd
    2 - 3875 - 247 - 1991 1889807
    also called variant 15/isoform a
    2 - 4521 - 247 - 1991 1889807
    also called variant 16/isoform a or IXabd
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainbasal nuclei  highly Homo sapiensAdult
     brainlimbic systemhippocampus   Homo sapiensAdult
     brainlimbic systemhippocampus highly Homo sapiensAdult
     brainforebraincerebral cortex highly Homo sapiensAdult
     brainhindbrainmedulla oblongata highly Homo sapiensAdult
     brainhindbraincerebellum highly Homo sapiensAdult
    Reproductivefemale systemplacenta  moderately Homo sapiensAdult
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiensAdult
    NervousSchawnn cell Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion in human milk
    at STAGE
    physiological period embryo
    Text anterior segment of the developing eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    isoforms Precursor synthesized as a precursor (pro-BDNF) (PMID: 19996106)
    HOMOLOGY
    interspecies ortholog to Bdnf, Mus musculus
    ortholog to Bdnf, Rattus norvegicus
    ortholog to bdnf, Danio rerio
    ortholog to BDNF, Pan troglodytes
    Homologene
    FAMILY
  • NGF beta family
  • CATEGORY transcription factor , signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • promoting the survival of neuronal cells located in the central nervous system or directly connected to it
  • supporting populations of sensory neurons via NRTK2 or NRTK3 signaling
  • involved in memory and hippocampal function
  • may be playing a role in the regulation and modulation of oocyte maturation
  • is a crucial signaling molecule between microglia and neurons
  • promoting the activation of CFL1 by reducing the phosphorylation of CFL1
  • promotes the maturation of cortical inhibition during early postnatal life, thereby regulating the critical period for visual cortical plasticity
  • critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells
  • responsible for inducing normal expression of the dopamine D3 receptor in nucleus accumbens both during development and in adulthood
  • an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences
  • involved in neurite outgrowth, early neuronal cell development, neuropeptide signaling/synthesis and neuronal receptor
  • regulating retinal growth cone filopodial dynamics through actin depolymerizing factor/cofilin CFL1
  • playing a role in energy homeostasis, as well as in cognitive function, memory, and behavior
  • plays a pivotal role in brain development and synaptic plasticity
  • with BDNF, are essential in promoting normal development of the central nervous system )
  • BDNF and NTRK2 play important roles in controlling respiration, movement, balance and feeding in the brainstem and that the NTRK2 is the most age-sensitive component of this system, especially in the hippocampus
  • important mediator of activity-dependent functions of the nervous system and its expression is dysregulated in several neuropsychiatric disorders
  • BDNF/TrkB signaling promotes neuronal survival and can help neurons resist toxic insults
  • secreted neurotrophin essential for the survival and differentiation of many neuronal populations, that serves as a self-amplifying autocrine factor in promoting axon formation in embryonic hippocampal neurons by triggering two nested positive-feedback mechanisms
  • protects endothelial progenitor cells by increasing expression of SOD2 thereby enhancing their antioxidant capacity
  • NR4A2 and BDNF show a similar expression pattern during postnatal cerebellar development
  • cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration
  • seems to be involved in regulation of synaptic plasticity and neurogenesis
  • expression of NTRK2 and BDNF is associated with poor prognosis in non-small cell lung cancer patients
  • is a key positive regulator of neural plasticity, promoting, for example, the actions of stimulant drugs of abuse such as cocaine, and is a negative modulator of morphine action
  • is necessary for ciliary localization of NTRK2 receptor and activation by BDNF
  • in the cochlar nucleus, NTF3 had a strong impact on enhancement of neuronal survival, whereas BDNF stimulated neuronal survival and axonal outgrowth
  • NTF3 and BDNF are critical for sensory neuron survival and establishment of neuronal projections to sensory epithelia in the embryonic inner ear
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    text neuron proliferation, differentiation and survival through its upstake at nerve terminals and retrograde transport to the cell body, also transported anterogradely, released on neuron depolarization
    PATHWAY
    metabolism
    signaling signal transduction
  • triggering rapid intracellular signals and action potentials in central neurons
  • BDNF/NTRK2 signaling activates PI3-kinase that promotes anterograde transport of NTRK2 in the putative axon, further enhancing local BDNF/NTRK2 signaling
  • EEF2K/EEF2 pathway is a key biochemical sensor that couple neuronal activity to spine plasticity, by controlling the dendritic translation of BDNF
  • signaling axis between BDNF and NFATC4 in adult hippocampal neural progenitor cells
  • a component
  • component of a heterodimer with NTF3
  • BDNF/NTRK2 signaling is essential for the development of photoreceptors and for synaptic communication between photoreceptors and second order retinal neurons
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • neurotrophin-3, NT-3 and nerve growth factor, NGF
  • TRKB
  • nitric oxide synthase, NOS
  • PSA-NCAM
  • ERalpha
  • CAPS2
  • Sortilin
  • REST-target gene
  • uses CREB1 and EGR3 to regulate NMDA receptor levels in cortical neurons
  • nuclear GNB2L1 is required to promote the transcription of the brain-derived neurotrophic factor (BDNF) 7)
  • PARD3 regulates RAC1 activation by BDNF but not by NRG1-Type III in Schwann cells, although both ligands activate RAC1
  • COMT on human cortical plasticity
  • progesterone-induced BDNF release was dependent on the expression of PGRMC1
  • SIK1 mediates the activation of MEF2-dependent transcription by BDNF
  • together with other epigenetic mechanisms, AICDA plays a key role in regulating activity-dependent BDNF expression in post-mitotic cortical neurons
  • BDNF induces the release of CYFIP1 from EIF4E, and this depends on MNKNK1
  • direct effect of ELAVL4 on regulating translation of dendritic BDNF mRNAs to mediate local and activity-dependent increases in dendritic BDNF synthesis
  • protective effects of BDNF against CRP-induced inflammation in women
  • BDNF, via truncated NTRK2, modulates SLC6A9 and SLC6A5 in astrocytes
  • LRIG1 physically interacts with NTRK2 and attenuates BDNF signaling
  • BDNF rescues ACTL6B-dependent synaptic plasticity and cocaine-associated memory in the nucleus accumbens
  • cell & other
    REGULATION
    induced by cortical neurons
    ASSOCIATED DISORDERS
    corresponding disease(s) WAGR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    low RNA and protein levels in brain of Alzheimer and Huntington disease patients
    constitutional     --low  
    reduced expression of brain-derived neurotrophic factor in the cerebrospinal fluid samples of infants with Ondine's curse
    constitutional     --low  
    in patients with major depressive disorder
    constitutional     --over  
    during migraine attacks, and in cluster headache, further supporting the involvement of BDNF in the pathophysiology of these primary headaches
    constitutional     --low  
    in the caudal nucleus of the solitary tract in the sudden infant death syndrome
    constitutional     --low  
    significant decrease in BDNF expression and impairment of downstream signaling in the aged hippocampus
    Susceptibility
  • to bipolar disorder and depression
  • to obsessive -compulsive disorder
  • to aberrant eating behaviors (anorexia and bulimia )
  • to obesity in WAGR
  • to Parkinson disease
  • to psychosis
  • to schizophrenia
  • to obesity
  • Variant & Polymorphism SNP
  • Val66Met is associated with alterations in brain anatomy and memory, and play a key role in genetic predispositions to anxiety and depressive disorders
  • VAL66MET increasing the risk of Parkinson disease and psychosis
  • associated to obesity risk
  • Candidate gene blood BDNF levels could be used as a biomarker to validate drugs aimed at restoring the defective intracellular vesicular dynamics in HD (Huntington disease)
    Marker
  • mature BDNF may serve as a biomarker for major depressive disorder
  • Therapy target
  • delivery of BDNF reverses the deficit in memory persistence caused by inhibition of hippocampal protein synthesis
  • SystemTypeDisorderPubmed
    neurology  
    manipulation of BDNF/TrkB signaling might have therapeutic efficacy in motor neuron diseases
    neurologyneurodegenerativealzheimer
    neuroprotective effects of entorhinal BDNF administration in animal models of Alzheimer's disease, with extension of therapeutic benefits into the degenerating hippocampus
    neurologyneurodegenerativealzheimer
    a potential therapy for Alzheimer's disease
    miscelleaneoussenescence 
    , epigenetic or pharmacological enhancement of BDNF-NTRK2 signaling could be a promising strategy for reversing cognitive aging
    ANIMAL & CELL MODELS
  • maturation of GABAergic innervation and inhibition was accelerated in mice in which the postnatal rise of brain-derived neurotrophic factor (BDNF) was accelerated and they showed a precocious development of visual acuity and an earlier termination of the critical period for ocular dominance plasticity
  • early postnatal lethality of BDNF null mice
  • heterozygous BDNF(+/-) mice develop enhanced intermale aggressiveness and hyperphagia accompanied by significant weight gain in early adulthood
  • transgenic overexpression of BDNF in mouse has a facilitatory effect on anxiety-like behavior, concomitant with increased spinogenesis in the basolateral amygdala and antidepressant effects
  • BDNF(Val66Met/Val66Met) mice exhibited increased anxiety-related behaviors in stressful settings