The FYN gene, a member of the protein-tyrosine kinase oncogene family, may be a therapeutic target for heroin use disorder according to a recent study published in Nature.
The researchers performed a genome-wide assessment of heroin users and matched controls to find direct molecular information about the addicted brain.
The researchers used post-mortem human brains from a cohort of White subjects who overdosed on heroin, as well as non-addicted controls. For the ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing), researchers studied 10 heroin-using subjects and 10 controls. Transcriptional profiling was performed using real-time quantitative polymerase chain reaction (qPCR) on 30 heroin-using subjects and 16 controls. Total FYN protein levels were assessed in 26 heroin users and 12 controls.
Using the ATAC-seq, the researchers found heroin affects chromatin (a substance within the chromosome that consists of DNA and protein) accessibility in the striatum. The drug also induces expression and activity of FYN kinase. It also leads to Tau phosphorylation in the striatum. This, combined with preclinical studies in rats, led the researchers to conclude that “FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder.”
Egervari G, Akpoyibo D, Rahman T, et al. Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder. Nat Commun. 2020 Sep 14;11(1):4634. doi: 10.1038/s41467-020-18114-3