Glutamate decarboxylase 1 (GAD1) (GAD1)

Glutamate decarboxylase 1 (GAD1), also known as GAD67, is a critical enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the vertebrate central nervous system (NCBI Gene: 2571). It catalyzes the decarboxylation of L-glutamate into GABA, primarily maintaining the basal levels of this neurotransmitter within the cytoplasm of GABAergic neurons (UniProt: P18088). GAD1 is one of two major isoforms, the other being GAD2 (GAD65), and it is distinguished by its widespread distribution throughout the cell body and its constitutive activity. Dysregulation of GAD1 expression or function is strongly linked to various neurological and psychiatric conditions, including schizophrenia, epilepsy, and bipolar disorder, where a deficit in GABAergic signaling is often observed (PMID: 12601104). Furthermore, GAD1 serves as a significant autoantigen in autoimmune disorders such as Stiff-person syndrome and Type 1 diabetes (PMID: 17617306). While few drugs target GAD1 directly as a primary mechanism, many anticonvulsants and anxiolytics aim to modulate the GABAergic pathway that GAD1 initiates. Understanding GAD1's role is essential for developing therapeutic strategies that restore the balance between excitatory and inhibitory neurotransmission.

Other names

GAD6767 kDa glutamic acid decarboxylaseGlutamate decarboxylase 67 kDa isoformCPSQ1

Catalyzes the alpha-decarboxylation of L-glutamate to form the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and carbon dioxide, utilizing pyridoxal 5'-phosphate (PLP) as a necessary cofactor (UniProt: P18088).