Excessive glutamate has been implicated in neurodegenerative disorders and stroke. One source of glutamate is from the hydrolysis of N-acetylaspartylglutamate (NAAG), a neurotransmitter found in the brain. NAAG can he hydrolysed by glutamate carboxypeptidase 2 (FOLH1), a membrane-bound, homodimeric enzyme which possesses both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity (Mesters et al. 2006). Inhibition of FOLH1 could have neuroprotective effects (Wozniak et al. 2012). Other dipeptidases able to hydrolyse NAAG are N-acetylated-alpha-linked acidic dipeptidase 2 (NAALAD2) (Pangalos et al. 1999, Hlouchova et al. 2009) and putative N-acetylated-alpha-linked acidic dipeptidase (FOLH1B) (O'Keefe et al. 2004).
Bekkers, M, Ashton, D, Fraiponts, E, Verhasselt, P, Gordon, RD, Somers, M, van der Helm, L, Neefs, JM, Pangalos, MN
Hilgenfeld, R, Tsukamoto, T, Barinka, C, Li, W, Slusher, BS, Mesters, JR, Konvalinka, J, Majer, P
O'Keefe, DS, Bacich, DJ, Heston, WD
Hlouchova, K, Barinka, C, Lubkowski, J, Konvalinka, J
Slusher, BS, Wu, Y, Wozniak, KM, Rojas, C
dipeptidase activity of NAALADases [plasma membrane]
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