Part:BBa_K5316006
hBDNF
BDNF is one of the most important endogenous proteins in controlling the survival, growth and differentiation of certain neuronal populations in both the peripheral nervous system and the central nervous system. Neurotrophins are a class of secreted proteins essential for the growth, differentiation, development, survival and recovery of the nervous system. BDNF neurotrophin-3 and neurotrophin-4/5 bind to high-affinity tyrosine kinase receptors TrkA, TrkB, TrkC as well as their low affinity receptor p75 NTR. Upon binding by neurotrophins, Trks form homodÃmers and their intracellular receptor tyrosine kinase domains autophosphorylates each other to initiate downstream cascades of signaling transduction which lead to protein regulation and functional changes in the cell. BDNF is the most abundant neurotrophic factor in the brain, and extensive studies have reported on its neuroprotective effects in various neurological disorders, including both neurodegenerative diseases and acute brain injuries. I have read many papers that claim BDNF to be the prime candidate for use as a stroke treatment. The prosurvival and neuroprotective functions of BDNF are mainly drawn from two signaling pathways activated by TrkB: - Phosphatidylinositol 3-kinase (PI3K)/Akt - Mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathways.
Design considerations
The iGEM Barcelona-UB team of 2024 adapted the original hBDNF sequence from Fulgenzi et al. to be Type IIS compatible.
BsaI.rc and SpaI.rc recognition sites, at positions 793 and 448 respectively, were removed by changing the codon to a synonym one, maintaining the amino acid and therefore its functionality.
References
Sequence sourced from: Nat Commun. 2020 Apr 23;11(1):1950: https://pubmed.ncbi.nlm.nih.gov/32327658/
BDNF functions and interaction pathways sourced from: Bali Med J. [S.l.], v. 5, n. 2, may 2016: https://ojs.unud.ac.id/index.php/bmj/article/download/21797/14420
| None |