Slc6a12, also known as betaine/GABA transporter-1 (BGT-1), is a neurotransmitter transporter that belongs to the solute carrier family 6. It is involved in GABAergic transmission, transporting GABA along with 3 Na+ and 1 Cl- ions per transport cycle, which is crucial for GABA homeostasis in the brain [2]. It may also have implications in processes related to neuronal development, synaptic function, and neural protein transport [3].

In a collagen-induced arthritis (CIA) mouse model, Slc6a12 inhibitors prevent sodium-induced activation of macrophage pyroptosis through the p38 MAPK/NF-κB signaling pathway, suggesting that high-salt intake-promoted RA progression is related to Slc6a12-mediated sodium transportation [1]. In Parkinson's disease (PD) in vitro models, inhibiting Slc6A12 expression enhanced neuronal growth and reduced cell apoptosis, indicating its potential role in PD's pathological process via the MAPK signaling pathway [3].

In conclusion, Slc6a12 is vital for GABAergic transmission and homeostasis. Its study in mouse models has revealed its roles in diseases such as rheumatoid arthritis and Parkinson's disease. These findings help understand the underlying mechanisms of these diseases and may offer potential therapeutic targets related to Slc6a12-mediated processes.

References:

1. Zhang, Xianzheng, Zhang, Ziwei, Zhao, Yuchen, Wang, Hua, Zhang, Lingling. 2024. Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12. In International journal of biological sciences, 20, 2922-2942. doi:10.7150/ijbs.93242. https://pubmed.ncbi.nlm.nih.gov/38904021/

2. Eskandari, Sepehr, Willford, Samantha L, Anderson, Cynthia M. . Revised Ion/Substrate Coupling Stoichiometry of GABA Transporters. In Advances in neurobiology, 16, 85-116. doi:10.1007/978-3-319-55769-4_5. https://pubmed.ncbi.nlm.nih.gov/28828607/

3. Peng, Haoran, Wu, Longyu, Chen, Siyuan, Yang, Hongqi, Li, Xue. 2024. Overexpression of solute carrier family 6 member 12 promotes cell injury in Parkinson's disease via MAPK signaling pathway. In Experimental gerontology, 194, 112484. doi:10.1016/j.exger.2024.112484. https://pubmed.ncbi.nlm.nih.gov/38871234/