S-Sulfocysteine

S-Sulfocysteine is an NMDA receptor agonist.¹ It is selective for the NMDA receptor over the AMPA receptor in radioligand binding assays (EC₅₀s = 8.2 and 59 µM, respectively). S-Sulfocysteine (200 µM) is cytotoxic to primary mouse neuronal cells.² It induces calcium influx and activates calpain-dependent degradation of the post-synaptic scaffolding protein gephyrin when used at a concentration of 100 µM. S-Sulfocysteine (2 mM) increases swimming and seizure-like movements, indicating neurodegeneration, in zebrafish larvae when administered three days post-fertilization.³ Urinary and plasma levels of S-sulfocysteine are increased in patients with molybdenum cofactor deficiency (MoCD), an inborn error of metabolism characterized by neurodegeneration and early childhood death.²

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1. Patneau, D.K. Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-ᴅ-aspartate and quisqualate receptors. J. Neurosci. 10(7), 2385-2399 (1990).

2. Kumar, A., Dejanovic, B., Hetsch, F., et al. S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. J. Clin. Invest. 127(12), 4365-4378 (2017).

3. Plate, J., Sassen, W.A., Hassan, A.H., et al. S-sulfocysteine induces seizure-like behaviors in zebrafish. Front. Pharmacol. 10, 122 (2019).