Homocysteine thiolactone

Homocysteine thiolactone (HTL) is an intramolecular thioester of homocysteine synthesized by methionyl-tRNA synthetase in an error-editing reaction that prevents translational incorporation of homocysteine into proteins. It can damage proteins through homocysteinylation of protein lysine residues. HTL has been reported to form isopeptide bonds with lysine residues in substrate proteins, a post-translational modification known as N-homocysteinylation (N-hcy). This causes protein damage via a thiyl radical mechanism.

When N-hcy hits α-syn, it exacerbates α-syn aggregation, neurotoxicity, and dopaminergic neuronal degeneration. It also damages the protein DJ-1, contributing to Parkinson's disease.