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Brain-derived neurotrophic factor and its clinical implications.

Bathina S, Das UN - Arch Med Sci (2015)

Bottom Line: It is widely expressed in the CNS, gut and other tissues.BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival.Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

View Article: PubMed Central - PubMed

Affiliation: Bio-Science Research Center, Gayatri Vidya Parishad College of Engineering, Visakhapatnam, India.

ABSTRACT
Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

No MeSH data available.


Related in: MedlinePlus

Gene structure of BDNF. Note the presence of four promoters in rat and 9 promoters in mouse. Each of the driving transcripts of BDNF mRNAs containing one of the four 5′ non-coding exons (I, II, III, IV) in promoters is later spliced to the common 3′ protein coding exon. Human BDNF structure and its splicing variant are seen above with arrows indicating alternative polyadenylation sites (PolyA) in the 3′-UTR and internal alternative splice sites in exons 2, 6, 7 and 9a (letters a, b, c and d) [18]. Arrangement of introns and exons on BDNF genes is determined by analyzing genomic and mRNA sequence using bioinformatics, RACE, and RT-PCR [17]
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Figure 0002: Gene structure of BDNF. Note the presence of four promoters in rat and 9 promoters in mouse. Each of the driving transcripts of BDNF mRNAs containing one of the four 5′ non-coding exons (I, II, III, IV) in promoters is later spliced to the common 3′ protein coding exon. Human BDNF structure and its splicing variant are seen above with arrows indicating alternative polyadenylation sites (PolyA) in the 3′-UTR and internal alternative splice sites in exons 2, 6, 7 and 9a (letters a, b, c and d) [18]. Arrangement of introns and exons on BDNF genes is determined by analyzing genomic and mRNA sequence using bioinformatics, RACE, and RT-PCR [17]

Mentions: BDNF has close structural homology to NGF and shares about 50% amino acid identity with NGF, NT-3 and NT-4/5. Each neurotrophin consists of a non-covalently linked homodimer with a signal peptide following the initiation codon and pro-region containing an N-linked glycosylation site [10–12]. In rats, the BDNF gene is located on chromosome 11 and is controlled by multiple activity-dependent and tissue-specific promoters I, II, III, IV; cAMP response-element binding protein (CREB) and upstream stimulatory factor-1/2 (USF-1/2) regulate promoters I and III, and calcium responsive transcription factor (CaRF) mediates transcription by binding to promoter III. All exons that have been defined in humans are also expressed in mouse and rat, except for human exons VIIB and VIII. The rat BDNF gene has been suggested to undergo cryptic splicing within exon II to form IIA, IIB and IIC genes [13–15]. The mouse BDNF gene has eight exons containing separate promoters upstream of each exon and one 3’ exon encodes the mature BDNF protein. Multiple promoters determine tissue-specific expression of the BDNF transcript [16]. Human BDNF structure is closely related to rat and mouse BDNF (Figure 2). Eight distinct mRNAs are transcribed, with transcripts containing exons I–III expressed predominantly in brain and exon IV found in lung and heart. In situ hybridization experiments have revealed that BDNF mRNA is strongly expressed in the brain. The BDNF expression levels are low during fetal development, markedly increase after birth, and then decrease in adults [17–19].


Brain-derived neurotrophic factor and its clinical implications.

Bathina S, Das UN - Arch Med Sci (2015)

Gene structure of BDNF. Note the presence of four promoters in rat and 9 promoters in mouse. Each of the driving transcripts of BDNF mRNAs containing one of the four 5′ non-coding exons (I, II, III, IV) in promoters is later spliced to the common 3′ protein coding exon. Human BDNF structure and its splicing variant are seen above with arrows indicating alternative polyadenylation sites (PolyA) in the 3′-UTR and internal alternative splice sites in exons 2, 6, 7 and 9a (letters a, b, c and d) [18]. Arrangement of introns and exons on BDNF genes is determined by analyzing genomic and mRNA sequence using bioinformatics, RACE, and RT-PCR [17]
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697050&req=5

Figure 0002: Gene structure of BDNF. Note the presence of four promoters in rat and 9 promoters in mouse. Each of the driving transcripts of BDNF mRNAs containing one of the four 5′ non-coding exons (I, II, III, IV) in promoters is later spliced to the common 3′ protein coding exon. Human BDNF structure and its splicing variant are seen above with arrows indicating alternative polyadenylation sites (PolyA) in the 3′-UTR and internal alternative splice sites in exons 2, 6, 7 and 9a (letters a, b, c and d) [18]. Arrangement of introns and exons on BDNF genes is determined by analyzing genomic and mRNA sequence using bioinformatics, RACE, and RT-PCR [17]
Mentions: BDNF has close structural homology to NGF and shares about 50% amino acid identity with NGF, NT-3 and NT-4/5. Each neurotrophin consists of a non-covalently linked homodimer with a signal peptide following the initiation codon and pro-region containing an N-linked glycosylation site [10–12]. In rats, the BDNF gene is located on chromosome 11 and is controlled by multiple activity-dependent and tissue-specific promoters I, II, III, IV; cAMP response-element binding protein (CREB) and upstream stimulatory factor-1/2 (USF-1/2) regulate promoters I and III, and calcium responsive transcription factor (CaRF) mediates transcription by binding to promoter III. All exons that have been defined in humans are also expressed in mouse and rat, except for human exons VIIB and VIII. The rat BDNF gene has been suggested to undergo cryptic splicing within exon II to form IIA, IIB and IIC genes [13–15]. The mouse BDNF gene has eight exons containing separate promoters upstream of each exon and one 3’ exon encodes the mature BDNF protein. Multiple promoters determine tissue-specific expression of the BDNF transcript [16]. Human BDNF structure is closely related to rat and mouse BDNF (Figure 2). Eight distinct mRNAs are transcribed, with transcripts containing exons I–III expressed predominantly in brain and exon IV found in lung and heart. In situ hybridization experiments have revealed that BDNF mRNA is strongly expressed in the brain. The BDNF expression levels are low during fetal development, markedly increase after birth, and then decrease in adults [17–19].

Bottom Line: It is widely expressed in the CNS, gut and other tissues.BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival.Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

View Article: PubMed Central - PubMed

Affiliation: Bio-Science Research Center, Gayatri Vidya Parishad College of Engineering, Visakhapatnam, India.

ABSTRACT
Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

No MeSH data available.


Related in: MedlinePlus