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Antigenic targets associated with the inhibitory synapse in patients with stiff-person syndrome

The presynaptic antigens are GAD (1), the enzyme that synthesizes GABA, the main inhibitory neurotransmitter, and amphiphysin (2), a synaptic vesicle protein responsible for endocytosis of plasma membranes following GABA release. Post-synaptically, the clinically relevant targets within the GAD-SD are gephyrin (3), a tubulin-binding protein needed for clustering both GABAA and glycine receptors; glycine receptor (4), a ligand-binding ion channel that allows the passage of chloride ions; and GABAA receptor–associated protein (GABARAP), a linker protein that promotes the organization of the GABAA receptors (Raju R, Rakocevic G, Chen Z, et al. Autoimmunity to GABAA-receptor-associated protein in stiff-person syndrome. Brain 2006;129[Pt 12]:3270-6). (Modified from: Dalakas MC. Progress and stiff challenges in understanding the role of GAD-antibodies in stiff-person syndrome. Exp Neurol 2013;247:303-7.)