Neuronostatin

Neuronostatin
Identifiers
SymbolNST
IUPHAR
CAS number1096485-24-3
HGNC11329
OMIMreferenced 182450, referenced
RefSeqassociated with SST 6750, associated with SST
Other data
LocusChr. 3 q27.3

Neuronostatin (abbreviated as NST) is a peptide hormone that may regulate portions of the endocrine system via interactions with G protein coupled receptor.

Neuronostatin is an alternative cleavage product of the preproprotein encoded by the somatostatin (SST) gene. Proteolytic processing of this precursor yields two distinct neuropeptides, with the specific products determined by tissue-dependent post-translational mechanisms. Neuronostatin is a linear, C-terminally amidated peptide that exists in forms of 13 or 19 amino acids in length. In contrast, somatostatin, another peptide derived from the same precursor, is structurally distinct, forming cyclic peptides of 14 or 28 amino acids. These differences arise from variations in cleavage sites and subsequent peptide modification, resulting in neuropeptides with unique amino acid sequences and conformations. Neuronostatin and somatostatin also differ in their biological distribution and relative abundance. Various tissues have been shown to express differing ratios of these peptides, reflecting tissue-specific regulation of SST gene processing and suggesting distinct physiological roles for each cleavage product.

Amino acid sequence alignment chart of SST and its cleavage products.

Neuronostatin has been associated with impaired memory, increased Aβ presence and aggravated Aβ pathologies, kidney function and breast/prostate cancer metastasis

Functions

Neuronostatin signals through the G protein Couple receptor 107(GPR107).

Neural tissues

Neuronostatin binds to monomeric Aβ1-42 and increases the presence of Aβ plaques within the cortex and hippocampus of APP/PS1 mice. Neuronostatin also affects proliferation rates and metabolism within neuronal cells via activation of GPR107 and PKA

Peripheral tissues

Neuronostatin/GPR107 signaling is associated with regulation of COL4 within both breast cancer and kidney tissues, where Neuronostatin/GPR107 reduces expression of COL4. In breast cancer, this reduction in COL4 generates enlarged pores within the extracellular matrix that allow for increase breast cancer migration and proliferation, leading to increased rates of metastasis. Neuronostatin and GPR107 have similarly been linked to increased rates of migration within prostate cancer. Within kidney tissues, Neuronostatin/GPR107 reduces thickening/remodeling of the glomerular basement membrane by reducing COL4 deposition and improves features of diabetic nephropathy

Additional features of Neuronostatin signaling include regulation of cardiomyocytes; Neuronostatin depresses cardiomyocyte function by affecting [Ca2+]i responses and regulating the expression of calcium regulating proteins

References

  1. 1 2 3 Yang S, Zhao X, Du Y, Yu P (August 2022). "Emerging functions of neuronostatin in physiology, pathology, and potential therapeutics". Neuropeptides. 94 102257. doi:10.1016/j.npep.2022.102257. PMID 35660860.
  2. 1 2 3 Samson WK, Zhang JV, Avsian-Kretchmer O, Cui K, Yosten GL, Klein C, et al. (November 2008). "Neuronostatin encoded by the somatostatin gene regulates neuronal, cardiovascular, and metabolic functions". The Journal of Biological Chemistry. 283 (46): 31949–31959. doi:10.1074/jbc.M804784200. PMC 2581552. PMID 18753129.
  3. ↑ Yang S, Shao T, Yu P, Cao R, Zhang M, Wen K, et al. (May 2019). "Neuronostatin promotes soluble Aβ1-42 oligomers -induced spatial learning and memory impairments in mice". Behavioural Brain Research. 364: 62–74. doi:10.1016/j.bbr.2019.01.047. PMID 30753874.
  4. 1 2 3 Yang S, Tang Q, Zhang Y, Du Y, Zhao X, Mei F, et al. (November 2024). "Neuronostatin regulates neuronal function and energetic metabolism in Alzheimer's disease in a GPR107-dependent manner". Neuropharmacology. 258 110090. doi:10.1016/j.neuropharm.2024.110090. PMID 39048031.
  5. 1 2 Yang S, Zhou F, Ma M, Yuan Y, Zhao S, Yu P (October 2020). "Neuronostatin Promotion Soluble Aβ1-42 Oligomers: Induced Dysfunctional Brain Glucose Metabolism in Mice". Neurochemical Research. 45 (10): 2474–2486. doi:10.1007/s11064-020-03106-y. PMID 32761296.
  6. 1 2 3 Xu D, Tong Z, Yang P, Chen Q, Wang S, Zhao W, et al. (February 2025). "G protein-coupled receptor 107 deficiency promotes development of diabetic nephropathy". Molecular Biomedicine. 6 (1) 10. doi:10.1186/s43556-025-00250-1. PMC 11814420. PMID 39932642.
  7. 1 2 3 Xu R, Liang J, Zhang S, Moru P, Liao K, Xu D, et al. (December 2025). "GPR107: A key driver of breast cancer invasion and metastasis through collagen IV modulation". Cancer Gene Therapy. 32 (12): 1414–1427. doi:10.1038/s41417-025-00977-7. PMID 41073571.
  8. 1 2 Sáez-Martínez P, Jiménez-Vacas JM, León-González AJ, Herrero-Aguayo V, Montero Hidalgo AJ, Gómez-Gómez E, et al. (June 2020). "Unleashing the Diagnostic, Prognostic and Therapeutic Potential of the Neuronostatin/GPR107 System in Prostate Cancer". Journal of Clinical Medicine. 9 (6): 1703. doi:10.3390/jcm9061703. PMC 7355908. PMID 32498336.
  9. ↑ Zhu X, Hu N, Chen X, Zhu MZ, Dong H, Xu X, et al. (2014). "Neuronostatin attenuates myocardial contractile function through inhibition of sarcoplasmic reticulum Ca2+-ATPase in murine heart". Cellular Physiology and Biochemistry. 33 (6): 1921–1932. doi:10.1159/000362969. PMID 25012062. Archived from the original on 2024-07-11.