Editing Brain-derived neurotrophic factor (section)

== Mechanism of action ==

BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, [[TrkB]] (pronounced "Track B") and the [[LNGFR]] (for ''low-affinity nerve growth factor receptor'', also known as p75).<ref name="pmid11399424">{{cite journal | vauthors = Patapoutian A, Reichardt LF | title = Trk receptors: mediators of neurotrophin action | journal = Current Opinion in Neurobiology | volume = 11 | issue = 3 | pages = 272–80 | date = June 2001 | pmid = 11399424 | doi = 10.1016/S0959-4388(00)00208-7 | s2cid = 8000523 }}</ref> It may also modulate the activity of various neurotransmitter receptors, including the [[Alpha-7 nicotinic receptor]].<ref name="pmid18495895">{{cite journal | vauthors = Fernandes CC, Pinto-Duarte A, Ribeiro JA, Sebastião AM | title = Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses in hippocampal interneurons | journal = The Journal of Neuroscience | volume = 28 | issue = 21 | pages = 5611–18 | date = May 2008 | pmid = 18495895 | pmc = 6670615 | doi = 10.1523/JNEUROSCI.5378-07.2008 }}</ref> BDNF has also been shown to interact with the [[reelin]] signaling chain.<!--

--><ref name="ReelinBook">{{cite journal | author = Fatemi, S. Hossein | title = Reelin glycoprotein: Structure, biology and roles in health and disease | date = 2005 | journal = Molecular Psychiatry | volume = 10 | issue = 3 | publisher = Springer | location = Berlin | pages = 251–7 | isbn = 978-0-387-76760-4 | doi = 10.1038/sj.mp.4001613| pmid = 15583703 | s2cid = 21206951 }}; see the chapter "A Tale of Two Genes: Reelin and BDNF"; pp. 237–45</ref><!--

--> The expression of reelin by [[Cajal–Retzius cell]]s goes down during development under the influence of BDNF.<!--

--><ref name="pmid9728912">{{cite journal | vauthors = Ringstedt T, Linnarsson S, Wagner J, Lendahl U, Kokaia Z, Arenas E, Ernfors P, Ibáñez CF | title = BDNF regulates reelin expression and Cajal-Retzius cell development in the cerebral cortex | journal = Neuron | volume = 21 | issue = 2 | pages = 305–15 | date = August 1998 | pmid = 9728912 | doi = 10.1016/S0896-6273(00)80540-1 | s2cid = 13983709 | doi-access = free }}</ref><!--

--> The latter also decreases reelin expression in neuronal culture.

=== TrkB ===

The TrkB receptor is encoded by the [[NTRK2]] gene and is member of a receptor family of tyrosine kinases that includes [[TrkA]] and [[TrkC]].  TrkB [[autophosphorylation]] is dependent upon its ligand-specific association with BDNF,<ref name="auto"/><ref name="auto1"/> a widely expressed activity-dependent neurotrophic factor that regulates [[Synaptic plasticity|plasticity]] and is dysregulated following [[Hypoxia (medical)|hypoxic]] injury. The activation of the BDNF-TrkB pathway is important in the development of short-term memory and the growth of neurons.{{citation needed|date=January 2016}}

=== LNGFR ===

The role of the other BDNF receptor, [[Low-affinity nerve growth factor receptor|p75]], is less clear. While the TrkB receptor interacts with BDNF in a ligand-specific manner, all neurotrophins can interact with the p75 receptor.<ref name="Bartkowska_2007">{{cite journal | vauthors = Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, Miller FD | title = Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development | journal = Development | volume = 134 | issue = 24 | pages = 4369–80 | date = December 2007 | pmid = 18003743 | doi = 10.1242/dev.008227 | doi-access = free }}</ref>  When the p75 receptor is activated, it leads to activation of [[NFkB]] receptor.<ref name="Bartkowska_2007"/>  Thus, neurotrophic signaling may trigger [[apoptosis]] rather than survival pathways in cells expressing the p75 receptor in the absence of Trk receptors.  Recent studies have revealed a truncated isoform of the TrkB receptor (t-TrkB) may act as a dominant negative to the p75 neurotrophin receptor, inhibiting the activity of p75, and preventing BDNF-mediated cell death.<ref name="pmid20955473">{{cite journal | vauthors = Michaelsen K, Zagrebelsky M, Berndt-Huch J, Polack M, Buschler A, Sendtner M, Korte M | title = Neurotrophin receptors TrkB.T1 and p75NTR cooperate in modulating both functional and structural plasticity in mature hippocampal neurons | journal = The European Journal of Neuroscience | volume = 32 | issue = 11 | pages = 1854–65 | date = December 2010 | pmid = 20955473 | doi = 10.1111/j.1460-9568.2010.07460.x | s2cid = 23496332 }}</ref>