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.[1] 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.[2]