Editing Brain-derived neurotrophic factor (section)

=== Val66Met ===
A common [[Single-nucleotide polymorphism|SNP]] in the BDNF gene is rs6265.<ref name=Baj2013>{{cite journal | vauthors = Baj G, Carlino D, Gardossi L, Tongiorgi E | title = Toward a unified biological hypothesis for the BDNF Val66Met-associated memory deficits in humans: a model of impaired dendritic mRNA trafficking | journal = Frontiers in Neuroscience | volume = 7 | pages = 188 | date = October 2013 | pmid = 24198753 | doi = 10.3389/fnins.2013.00188 | pmc=3812868| doi-access = free }}</ref>  This point mutation in the coding sequence, a guanine to adenine switch at position 196, results in an amino acid switch: valine to methionine exchange at codon 66, Val66Met, which is in the prodomain of BDNF.<ref name=Baj2013/><ref name="Bath_2006"/> Val66Met is unique to humans.<ref name=Baj2013/><ref name="Bath_2006"/>

The mutation interferes with normal translation and intracellular trafficking of BDNF mRNA, as it destabilizes the mRNA and renders it prone to degradation.<ref name=Baj2013/>  The proteins resulting from mRNA that does get translated, are not trafficked and secreted normally, as the amino acid change occurs on the portion of the prodomain where [[Sortilin 1|sortilin]] binds; and sortilin is essential for normal trafficking.<ref name=Baj2013/><ref name="Bath_2006"/><ref>{{cite journal | vauthors = Cunha C, Brambilla R, Thomas KL | title = A simple role for BDNF in learning and memory? | journal = Frontiers in Molecular Neuroscience | volume = 3 | pages = 1 | date = 2010-01-01 | pmid = 20162032 | pmc = 2821174 | doi = 10.3389/neuro.02.001.2010 | doi-access = free }}</ref>

The Val66Met mutation results in a reduction of hippocampal tissue and has since been reported in a high number of individuals with learning and memory disorders,<ref name="Bath_2006"/> [[anxiety disorder]]s,<ref name=Dincheva2016rev>{{cite journal | vauthors = Dincheva I, Lynch NB, Lee FS | title = The Role of BDNF in the Development of Fear Learning | journal = Depression and Anxiety | volume = 33 | issue = 10 | pages = 907–916 | date = October 2016 | pmid = 27699937 | pmc = 5089164 | doi = 10.1002/da.22497 }}</ref> [[Major depressive disorder|major depression]],<ref>{{cite journal | vauthors = Youssef MM, Underwood MD, Huang YY, Hsiung SC, Liu Y, Simpson NR, Bakalian MJ, Rosoklija GB, Dwork AJ, Arango V, Mann JJ | title = Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide | journal = The International Journal of Neuropsychopharmacology | volume = 21 | issue = 6 | pages = 528–538 | date = June 2018 | pmid = 29432620 | pmc = 6007393 | doi = 10.1093/ijnp/pyy008 }}</ref> and neurodegenerative diseases such as Alzheimer's and [[Parkinson's disease|Parkinson's]].<ref>{{cite journal | vauthors = Lu B, Nagappan G, Guan X, Nathan PJ, Wren P | title = BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases | journal = Nature Reviews. Neuroscience | volume = 14 | issue = 6 | pages = 401–16 | date = June 2013 | pmid = 23674053 | doi = 10.1038/nrn3505 | s2cid = 2065483 }}</ref>

A meta-analysis indicates that the BDNF Val66Met variant is not associated with serum BDNF.<ref>{{cite journal | vauthors = Terracciano A, Piras MG, Lobina M, Mulas A, Meirelles O, Sutin AR, Chan W, Sanna S, Uda M, Crisponi L, Schlessinger D | title = Genetics of serum BDNF: meta-analysis of the Val66Met and genome-wide association study | journal = The World Journal of Biological Psychiatry | volume = 14 | issue = 8 | pages = 583–89 | date = December 2013 | pmid = 22047184 | pmc = 3288597 | doi = 10.3109/15622975.2011.616533 }}</ref>