Vogel, K. R.; Ainslie, G. R.; Jansen, E. E. W.; Salomons, G. S.; Gibson, K. M. published the artcile< Therapeutic relevance of mTOR inhibition in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism>, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is torin mTOR succinate semialdehyde dehydrogenase deficiency GABA oxidataive stress; GABA; Oxidative stress; Succinic semialdehyde dehydrogenase deficiency; Torin 1; Torin 2; mTOR.
Aldehyde dehydrogenase 5a1-deficient (aldh5a1-/-) mice, the murine orthologue of human succinic semialdehyde dehydrogenase deficiency (SSADHD), manifest increased GABA (4-aminobutyric acid) that disrupts autophagy, increases mitochondria number, and induces oxidative stress, all mitigated with the mTOR (mechanistic target of rapamycin) inhibitor rapamycin [1]. Because GABA regulates mTOR, we tested the hypothesis that aldh5a1-/- mice would show altered levels of mRNA for genes associated with mTOR signaling and oxidative stress that could be mitigated by inhibiting mTOR. We observed that multiple metabolites associated with GABA metabolism (γ-hydroxybutyrate, succinic semialdehyde, D-2-hydroxyglutarate, 4,5-dihydrohexanoate) and oxidative stress were significantly increased in multiple tissues derived from aldh5a1-/- mice. These metabolic perturbations were associated with decreased levels of reduced glutathione (GSH) in brain and liver of aldh5a1-/- mice, as well as increased levels of adducts of the lipid peroxidation byproduct, 4-hydroxy-2-nonenal (4-HNE). Decreased liver mRNA levels for multiple genes associated with mTOR signaling and oxidative stress parameters were detected in aldh5a1-/- mice, and several were significantly improved with the administration of mTOR inhibitors (Torin 1/Torin 2). Western blot anal. of selected proteins corresponding to oxidative stress transcripts (glutathione transferase, superoxide dismutase, peroxiredoxin 1) confirmed gene expression findings. Our data provide addnl. preclin. evidence for the potential therapeutic efficacy of mTOR inhibitors in SSADHD.
Biochimica et Biophysica Acta, Molecular Basis of Disease published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Name: 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem