Glutamic acid decarboxylase 2 (GAD2), or GAD65, is encoded by the GAD2 gene on chromosome 10q25.3. It consists of 585 amino acids with a molecular weight of approximately 65 kDa. GAD2 undergoes various post-translational modifications, including phosphorylation, glycosylation, and the formation of disulfide bonds. It is primarily an intracellular protein found in the cytoplasm and synaptic vesicles of neurons.
The main function of GAD2 is to catalyze the conversion of glutamate to gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. GABA plays a crucial role in regulating neuronal excitability and synaptic transmission and maintaining the balance between excitation and inhibition in the brain. Expression of GAD2 is predominantly observed in neurons of the central nervous system, particularly in GABAergic neurons, which utilize GABA as a neurotransmitter. Various factors, including neuronal activity, neurotransmitters, and transcription factors, regulate the expression of GAD2. Interestingly, mutations or dysregulation of GAD2 have been associated with several neurological disorders, including epilepsy, schizophrenia, and Parkinson’s disease. Additionally, autoantibodies targeting GAD2 have been implicated in autoimmune diseases such as type 1 diabetes mellitus and stiff-person syndrome.
The expression has been extensively studied in various diseases, notably autoimmune disorders like type 1 diabetes and autoimmune neurological conditions such as epilepsy and movement disorders. In type 1 diabetes, autoantibodies targeting GAD2 are instrumental as diagnostic markers, aiding in the identification of individuals at risk and facilitating early disease detection. Similarly, in autoimmune neurological disorders like stiff person syndrome and autoimmune encephalitis, GAD2 autoantibodies serve as biomarkers, indicating autoimmune-mediated neuronal damage. While GAD2 expression itself may not directly influence prognosis in cancer or diseases beyond autoimmune disorders, the presence of GAD2 autoantibodies can offer insights into disease severity and predict response to immunomodulatory therapies. Moreover, in neurological disorders such as epilepsy and movement disorders, GAD2 expression patterns in specific brain regions may hold significance for disease progression and treatment response, highlighting potential therapeutic targets.
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Synonyms
Glutamate decarboxylase 2, 65 kDa glutamic acid decarboxylase, Glutamate decarboxylase 65 kDa isoform, DCE2; GAD2; Glutamic Acid Decarboxylase 2 (Pancreas); Glutamic Acid Decarboxylase 2 (Pancreatic Islets and Brain 65kDa); Glutamic Acid Decarboxylase 65 (GAD65)
Research Areas
Cardiovascular, Neuroscience, Neural Stem Cells, Transcription Factors
