PMID- 38155909
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - GABA(A) receptors as plausible molecular targets and mediators for taurine and 
      homotaurine actions.
PG  - 1271203
LID - 10.3389/fphar.2023.1271203 [doi]
LID - 1271203
AB  - Dementia and autoimmune diseases are prevalent conditions with limited treatment 
      options. 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. HT is a blood-brain barrier permeable drug under investigation 
      for Alzheimer's disease. HT also has beneficial effects in a mouse model of 
      multiple sclerosis likely through an anti-inflammatory mechanism mediated by 
      GABA(A) receptor (GABA(A)R) agonism in immune cells. While both taurine and HT 
      are structural GABA analogs and thought to be GABA mimetics at GABA(A)Rs, there 
      is uncertainty concerning their potency as GABA mimetics on native GABA(A)Rs. We 
      show that HT is a very potent GABA mimetic, as it evokes GABA(A)R-mediated 
      currents with an EC(50) of 0.4 muM (vs. 3.7 muM for GABA and 116 microM for taurine) in 
      murine cerebellar granule cells in brain slices, with both taurine and HT having 
      similar efficacy in activating native GABA(A)Rs. Furthermore, HT displaces the 
      high affinity GABA(A)R ligand [(3)H]muscimol at similarly low concentrations (HT 
      IC(50) of 0.16 muM vs. 125 muM for taurine) in mouse brain homogenates. The potency 
      of taurine and HT as GABA(A)R 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. Consequently, we discuss 
      that GABA(A)Rs 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.
CI  - Copyright (c) 2023 Meera, Uusi-Oukari, Lipshutz and Wallner.
FAU - Meera, Pratap
AU  - Meera P
AD  - Department of Neurobiology, University of California, Los Angeles, Los Angeles, 
      CA, United States.
FAU - Uusi-Oukari, Mikko
AU  - Uusi-Oukari M
AD  - Integrative Physiology and Pharmacology, Institute of Biomedicine, University of 
      Turku, Turku, Finland.
FAU - Lipshutz, Gerald S
AU  - Lipshutz GS
AD  - Department of Surgery, University of California, Los Angeles, Los Angeles, CA, 
      United States.
AD  - Molecular and Medical Pharmacology, University of California, Los Angeles, Los 
      Angeles, CA, United States.
AD  - Intellectual and Developmental Disabilities Research Center, University of 
      California, Los Angeles, Los Angeles, CA, United States.
AD  - Semel Institute for Neuroscience, University of California, Los Angeles, Los 
      Angeles, CA, United States.
FAU - Wallner, Martin
AU  - Wallner M
AD  - Department of Surgery, University of California, Los Angeles, Los Angeles, CA, 
      United States.
LA  - eng
GR  - R01 NS100979/NS/NINDS NIH HHS/United States
GR  - R01 NS110596/NS/NINDS NIH HHS/United States
GR  - R03 NS114623/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20231214
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10752957
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - GABA-mimetics
OT  - GABAA receptor
OT  - homotaurine
OT  - inflammation
OT  - taurine
OT  - tramiprosate
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/01/02 10:02
MHDA- 2024/01/02 10:03
PMCR- 2023/12/14
CRDT- 2023/12/29 03:42
PHST- 2023/08/01 00:00 [received]
PHST- 2023/11/20 00:00 [accepted]
PHST- 2024/01/02 10:03 [medline]
PHST- 2024/01/02 10:02 [pubmed]
PHST- 2023/12/29 03:42 [entrez]
PHST- 2023/12/14 00:00 [pmc-release]
AID - 1271203 [pii]
AID - 10.3389/fphar.2023.1271203 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Dec 14;14:1271203. doi: 10.3389/fphar.2023.1271203. 
      eCollection 2023.