Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms

Abstract

Taurine is a sulfur-containing amino acid and known as semi-essential in mammals and is produced chiefly by the liver and kidney. It presents in different organs, including retina, brain, heart and placenta and demonstrates extensive physiological activities within the body. In the several disease models, it attenuates inflammation- and oxidative stress-mediated injuries. Taurine also modulates ER stress, Ca²⁺ homeostasis and neuronal activity at the molecular level as part of its broader roles. Different cellular processes such as energy metabolism, gene expression, osmosis and quality control of protein are regulated by taurine. In addition, taurine displays potential ameliorating effects against different neurological disorders such as neurodegenerative diseases, stroke, epilepsy and diabetic neuropathy and protects against injuries and toxicities of the nervous system. Several findings demonstrate its therapeutic role against neurodevelopmental disorders, including Angelman syndrome, Fragile X syndrome, sleep-wake disorders, neural tube defects and attention-deficit hyperactivity disorder. Considering current biopharmaceutical limitations, developing novel delivery approaches and new derivatives and precursors of taurine may be an attractive option for treating neurological disorders. Herein, we present an overview on the therapeutic potential of taurine against neurological disorders and highlight clinical studies and its molecular mechanistic roles. This article also addresses the neuropharmacological potential of taurine analogs.

Keywords: Analogs; Clinical study and Neurological disorders; Molecular role; Taurine; Therapeutic.

Graphical abstract

Fig. 1

Neuroprotective effects of taurine against ER stress pathways. During ER stress, three types of ER membrane receptors (PERK, ATF6 and IRE1) located at the ER membrane are activated. Phosphorylated PERK converts eIF2α to phosphorylated eIF2α, which activates ATF4, which translocates to the nucleus and transcribes CHOP. ATF6 is converted to its active form, cleaved ATF6, which also transcribes CHOP. IRE1 is activated by phosphorylation and ultimately potentiates the expression of CHOP. Caspase-12, located on the outer surface of the ER membrane, is cleaved into its active form, which facilitates caspase cascade apoptosis. Taurine exerts neuroprotective effects by inhibiting the activation of PERK, ATF6, IRE1, and caspase-12.

Fig. 2

Taurine-mediated neuroprotection against glutamate-induced neuronal death. Taurine activated both ionotropic taurine receptor (iTauR) and metabotropic taurine receptor (mTauR). Upon binding with these receptors, activated iTauR inhibits the reverse mode of sodium/calcium exchangers, as well as inhibits voltage-gated calcium channels (VGCC), leads to decreased intracellular calcium. Activated mTauR also decreases IP3 production, which attenuates the release of calcium from the endoplasmic reticulum (ER). As a result, decreases in intracellular calcium inhibit calpain, which ultimately blocks the conformational changes of Bcl-2 and Bax. This inhibits activation of Bax homodimers that target the mitochondrion-mediated neuronal death cascade.

Fig. 3

Delivery prospects of taurine for targeting the blood-brain barrier and acting on target sites. This figure proposes that taurine prodrugs may be converted into taurine upon crossing the BBB. Taurine derivatives may be capable of producing action via crossing BBB either forming taurine or their own forms. Novel formulations may be capable of crossing the BBB due to their lipophilic nature and acting on the target site.