PSMA (Prostate specific membrane antigen, Glutamate carboxypeptidase II)

Prostate specific membrane antigen (PSMA), also known as Glutamate carboxypeptidase II (GCPII), is a type II transmembrane glycoprotein that belongs to the M28 peptidase family. It acts as a glutamate carboxypeptidase on different substrates such as folate as well as the neuropeptide N-acetyl-l-aspartyl-l-glutamate. PSMA is expressed in a number of tissues including prostate, kidney, and both the central and peripheral nervous systems. A mutation in this gene is associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and subsequent hyperhomocysteinemia. Expression of PSMA in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity.

Western Blot: PSMA Antibody

In addition, PSMA is an established cancer marker. In particular, it is upregulated in prostate cancer and has proven to be an effective diagnostic and prognostic indicator of cancer. Labeling experiments using a PSMA antibody allowed Sacha’s group to map expression of GCPII within the human brain to better research its potential as a therapeutic target for neurotoxic glutamate-based diseases such as ALS, Huntington’s, epilepsy, and Alzheimer’s disease (AD)¹. The same group also used the PSMA antibody in follow-up domain mapping studies where they identified N- and C-termini regions responsible for enzymatic activity and proper folding². Studies out of Rovenska’s group focused on analyzing the utility of rat and pig animal models for enzyme and in vivo disease studies³. They employed the PSMA antibody in immunoblotting and determined that while the other species orthologs were suitable for enzyme studies, diffuse and variation expression patterns were limitations for their use in drug discovery. The PSMA antibody was used to validate the utility of performing multiplex antibody epitope mapping with a bacterial cell-surface display system⁴. Additionally, tissue microarrays analyzed with the PSMA antibody allowed Jaraj et al to determine the expression of glutamate decarboxylase 1 (GAD1) in benign and metastatic prostatic tissue⁵. GAD1 has potential as a prostate-specific tissue biomarker.