TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease.

摘要: Protein S-palmitoylation, the covalent lipid modification of side chain Cys residues with 16‑carbon fatty acid palmitate, is most common acylation, and it enhances membrane stability ion channels. This post-translational (PTM) determines a functional mechanism channel life cycle from maturation trafficking to localization. Especially, neurodevelopment regulated by balancing level synaptic protein palmitoylation/depalmitoylation. Recently, we revealed pathological role transient receptor potential canonical type 5 (TRPC5) in striatal neuronal loss during Huntington's disease (HD), which abnormally activated oxidative stress. Here, report TRPC5 palmitoylation at conserved cysteine residue, that critical for intrinsic activity. Furthermore, identified therapeutic effect depalmitoylation enhancing instability on HD cells order lower toxicity. Collectively, these findings suggest controlling S-palmitoylation as risk factor can modulate expression activity, providing new insights into strategy neurodegenerative diseases.