![]() Taurine is a highly abundant non-proteinogenic amino acid with a multitude of proposed biological functions ( Huxtable, 1992 Warskulat et al., 2007), including agonist actions on GABA A and glycine receptors ( Albrecht and Schousboe, 2005 Jia et al., 2008). Activation of these immune cell GABA ARs could provide a plausible explanation why classical GABA ARs agonists (alcohol, barbiturates and anesthetics like etomidate and propofol) exert anti-inflammatory, immunosuppressive actions ( Wheeler et al., 2011 Prud’homme et al., 2015 Szabo and Saha, 2015), and also why moderate alcohol consumption is protective against autoimmune disease ( Azizov et al., 2020). While GABA is the main inhibitory neurotransmitter in the mammalian brain with actions primarily mediated by ionotropic GABA A receptors (GABA ARs), there is growing evidence of pharmacologically similar GABA ARs expressed in immune cells ( Bhandage and Barragan, 2021 Kang et al., 2022 Tian and Kaufman, 2023). Consequently, we discuss that GABA ARs subtypes, similar to the ones we studied here in neurons, are plausible targets for mediating the potential beneficial effects of taurine in health and life-span extension and the beneficial HT effects in dementia and autoimmune conditions. The potency of taurine and HT as GABA AR agonists aligns with endogenous concentrations of taurine in the blood and with HT concentrations achieved in the brain following oral administration of HT or the HT pro-drug ALZ-801. 125 μM for taurine) in mouse brain homogenates. Furthermore, HT displaces the high affinity GABA AR ligand muscimol at similarly low concentrations (HT IC 50 of 0.16 μM vs. 3.7 μM for GABA and 116 µM for taurine) in murine cerebellar granule cells in brain slices, with both taurine and HT having similar efficacy in activating native GABA ARs. We show that HT is a very potent GABA mimetic, as it evokes GABA AR-mediated currents with an EC 50 of 0.4 μM (vs. While both taurine and HT are structural GABA analogs and thought to be GABA mimetics at GABA ARs, there is uncertainty concerning their potency as GABA mimetics on native GABA ARs. HT also has beneficial effects in a mouse model of multiple sclerosis likely through an anti-inflammatory mechanism mediated by GABA A receptor (GABA AR) agonism in immune cells. HT is a blood-brain barrier permeable drug under investigation for Alzheimer’s disease. ![]() Taurine and homotaurine (HT) are naturally occurring sulfonate amino acids, with taurine being highly abundant in animal tissues, but declining with age in the blood.
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