Neurogranin

Neurogranin is a calmodulin-binding protein expressed primarily in the brain, particularly in dendritic spines, and participating in the protein kinase C signaling pathway. Neurogranin is the main postsynaptic protein regulating the availability of calmodulin, binding to it in the absence of calcium. Phosphorylation by protein kinase C lowers its binding ability. NRGN gene expression is controlled by thyroid hormones.[1] Human neurogranin consists of 78 amino acids.

neurogranin (protein kinase C substrate, RC3)
Identifiers
SymbolNRGN
NCBI gene4900
HGNC8000
OMIM602350
RefSeqNM_006176
UniProtQ92686
Other data
LocusChr. 11 q24

One study tells of potential link of neurogranin gene to the heightened risk of schizophrenia in males,[2] another study gives evidence of lowered neurogranin immunoreactivity in the brains of people suffering from schizophrenia.[3]

Neurogranin concentration in cerebrospinal fluid (CSF) is further discussed as marker for synaptic dysfunction in age-related neurodegeneration.[4] It has also been shown to be specifically increased in patients with Alzheimer’s disease.[5][6] Especially the ratio of CSF neurogranin trunc P75 and the beta-secretase BACE1 is suggested as potential marker for cognitive deterioration in the progress of Alzheimer’s disease.[7]

Prior to its identification in the bovine and rat brain in 1991,[8] neurogranin was known as a putative protein kinase C-phosphorylated protein named p17. Human neurogranin was cloned in 1997 and turned out to be 96% identical to the rat protein.[9]

References
  1. Martínez de Arrieta C, Morte B, Coloma A, Bernal J (January 1999). "The human RC3 gene homolog, NRGN contains a thyroid hormone-responsive element located in the first intron". Endocrinology. 140 (1): 335–43. doi:10.1210/en.140.1.335. PMID 9886843.
  2. Ruano D, Aulchenko YS, Macedo A, Soares MJ, Valente J, Azevedo MH, et al. (January 2008). "Association of the gene encoding neurogranin with schizophrenia in males". Journal of Psychiatric Research. 42 (2): 125–33. doi:10.1016/j.jpsychires.2006.10.008. PMID 17140601.
  3. Broadbelt K, Ramprasaud A, Jones LB (October 2006). "Evidence of altered neurogranin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex". Schizophrenia Research. 87 (1–3): 6–14. doi:10.1016/j.schres.2006.04.028. PMID 16797925.
  4. Casaletto KB, Elahi FM, Bettcher BM, Neuhaus J, Bendlin BB, Asthana S, et al. (October 2017). "Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers". Neurology. 89 (17): 1782–1788. doi:10.1212/WNL.0000000000004569. PMC 5664306. PMID 28939668.
  5. De Vos A, Jacobs D, Struyfs H, Fransen E, Andersson K, Portelius E, et al. (December 2015). "C-terminal neurogranin is increased in cerebrospinal fluid but unchanged in plasma in Alzheimer's disease". Alzheimer's & Dementia. 11 (12): 1461–1469. doi:10.1016/j.jalz.2015.05.012. PMID 26092348.
  6. Willemse EA, De Vos A, Herries EM, Andreasson U, Engelborghs S, van der Flier WM, et al. (June 2018). "Neurogranin as Cerebrospinal Fluid Biomarker for Alzheimer Disease: An Assay Comparison Study". Clinical Chemistry. 64 (6): 927–937. doi:10.1373/clinchem.2017.283028. PMID 29523639.
  7. De Vos A, Struyfs H, Jacobs D, Fransen E, Klewansky T, De Roeck E, et al. (July 2016). "The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer's Disease". Journal of Alzheimer's Disease. 53 (4): 1523–38. doi:10.3233/JAD-160227. PMC 4981899. PMID 27392859.
  8. Baudier J, Deloulme JC, Van Dorsselaer A, Black D, Matthes HW (January 1991). "Purification and characterization of a brain-specific protein kinase C substrate, neurogranin (p17). Identification of a consensus amino acid sequence between neurogranin and neuromodulin (GAP43) that corresponds to the protein kinase C phosphorylation site and the calmodulin-binding domain". The Journal of Biological Chemistry. 266 (1): 229–37. PMID 1824695.
  9. Martínez de Arrieta C, Pérez Jurado L, Bernal J, Coloma A (April 1997). "Structure, organization, and chromosomal mapping of the human neurogranin gene (NRGN)". Genomics. 41 (2): 243–9. doi:10.1006/geno.1997.4622. PMID 9143500.
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