GAD65s

GAD65 refers to Glutamate Decarboxylase 65 kDa. It is one of two common isoforms of the enzyme glutamate decarboxylase (GAD) found in mammals. GAD65, along with its counterpart GAD67, is responsible for catalyzing the conversion of glutamate, an excitatory neurotransmitter, into gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. This conversion is a critical step in regulating neuronal excitability in the central nervous system.

GAD65 is primarily found in presynaptic terminals of GABAergic neurons. Its expression is particularly concentrated in the nerve terminals where it plays a role in the synthesis and packaging of GABA into synaptic vesicles. This isoform is known to be activated by phosphorylation and is considered a rate-limiting enzyme in GABA synthesis under certain physiological conditions.

Autoantibodies against GAD65 are of significant clinical interest. These autoantibodies are strongly associated with certain autoimmune neurological disorders, most notably stiff-person syndrome (SPS). In SPS, the immune system mistakenly attacks GAD65, leading to impaired GABAergic inhibition and resulting in muscle rigidity and spasms. GAD65 antibodies are also detected in some individuals with type 1 diabetes and other autoimmune conditions, suggesting a broader role in autoimmune pathogenesis. Detecting these antibodies in serum can aid in the diagnosis and understanding of these conditions.