Editing Brain-derived neurotrophic factor (section)

== BDNF-AS ==

The genomic locus encoding BDNF is structurally complex and also encodes BDNF-antisense (BDNF-AS; also known as BDNFOS or ANTI-BDNF).<ref name="Lipovich_2012">{{cite journal | vauthors = Lipovich L, Dachet F, Cai J, Bagla S, Balan K, Jia H, Loeb JA | title = Activity-dependent human brain coding/noncoding gene regulatory networks | journal = Genetics | volume = 192 | issue = 3 | pages = 1133–1148 | date = November 2012 | pmid = 22960213 | pmc = 3522156 | doi = 10.1534/genetics.112.145128 | doi-access = free }}</ref><ref name="Shkundin_2023">{{cite journal | vauthors = Shkundin A, Halaris A | title = Associations of BDNF/BDNF-AS SNPs with Depression, Schizophrenia, and Bipolar Disorder | journal = Journal of Personalized Medicine| volume = 13 | issue = 9 | pages = 1395 | date = September 18, 2023 | doi = 10.3390/jpm13091395 | pmc = 10533016 | pmid = 37763162 | doi-access = free }}</ref><ref name="Pruunsild_2007">{{cite journal | vauthors = Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T | title = Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters | journal = Genomics | volume = 90 | issue = 3 | pages = 397–406 | date = September 2007 | pmc = 2568880 | pmid = 17629449 | doi = 10.1016/j.ygeno.2007.05.004 | doi-access = free }}</ref> BDNF-AS is a long non-coding RNA (lncRNA) transcribed from the opposite strand of the BDNF gene.<ref name="Shkundin_2023"/> This lncRNA was identified in 2005 through searches in expressed sequence tag (EST) databases and subsequent RT-PCR experiments.<ref name="Ghafouri-Fard_2021">{{cite journal | vauthors = Ghafouri-Fard S, Khoshbakht T, Taheri M, Ghanbari M | title = A concise review on the role of BDNF-AS in human disorders | journal = Biomedicine & Pharmacotherapy | volume = 142 | pages = 112051 | date = October 2021 | doi = 10.1016/j.biopha.2021.112051 | pmid = 34426254 | doi-access = free }}</ref><ref name="Liu_2005">{{cite journal | vauthors = Liu QR, Walther D, Drgon T, Polesskaya O, Lesnick TG, Strain KJ, de Andrade M, Bower JH, Maraganore DM, Uhl GR | title = Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's Disease | journal = American Journal of Medical Genetics | volume = 134B | issue = 1 | pages = 93–103 | date = April 5, 2005 | doi = 10.1002/ajmg.b.30109 | pmid = 15666411 }}</ref> The gene encoding BDNF-AS is located on chromosome 11p14.1.<ref name="Ghafouri-Fard_2021"/> BDNF mRNA and BDNF-AS share a common overlapping region and form double-stranded RNA (dsRNA) duplexes.<ref name="Shkundin_2023"/><ref name="Pruunsild_2007"/>

BDNF-AS regulates BDNF expression and can suppress BDNF mRNA.<ref name="Shkundin_2023"/> In the human neocortex, regions with increased activity and BDNF expression exhibit reduced BDNF-AS expression.<ref name="Lipovich_2012"/> Elevated BDNF-AS levels are associated with reduced BDNF expression and have been shown to promote neurotoxicity, increase apoptosis, and decrease cell viability.<ref name="Shkundin_2023"/> Conversely, inhibiting BDNF-AS upregulates BDNF mRNA, activates BDNF-mediated signaling pathways, increases BDNF protein levels, suppresses neuronal apoptosis, and promotes neuronal outgrowth and differentiation.<ref name="Shkundin_2023"/>

The BDNF-AS gene consists of 10 exons and a functional promoter upstream of exon 1. The BDNF-AS gene generates numerous distinct non-coding RNAs through alternative splicing. This diversity of spliced isoforms is a common feature of eukaryotic organisms, particularly in the nervous system.<ref name="Pruunsild_2007"/> Notably, BDNF-AS is absent in rodents, although highly homologous sequences are present in the genomes of chimpanzees and rhesus monkeys, suggesting a primate/hominid evolutionary origin of BDNF-AS.<ref name="Pruunsild_2007"/>

Variations in both the BDNF and BDNF-AS genes are important factors to consider, given their potential to alter BDNF function and contribute to multiple human phenotypes influencing disease susceptibility and treatment outcomes.<ref name="Shkundin_2023"/>