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The dipeptide carnosine is a bioactive endogenously abundant peptide. High amounts of carnosine are found in muscle and brain tissues. A Russian scientist with the name of Vladimir Sergeevich Gulevish is credited to discover carnosine for the first time in mammalian muscle. Gulevich also discovered a number of new nitrogen compounds in muscle, including carnosine, carnitine, and anserine. Although carnosine is a natural dipeptide, the peptide can be synthesized using Fmoc-chemistry based solid phase peptide synthesis (SPPS).
Carnosine is a zwitterion. Zwitterions are neutral molecules that have a positive and negative charge. Carnosine can be analyzed in an amino acid analyzer as the dipeptide or hydrolyzed into the two amino acids β–alanine and L-histidine. Mass spectrometry, especially LC-MS(MS) offers itself as well as a sensitive tool for its detection and analysis.
High rates of carnosine synthesis are thought to occur in glial cells, not in neurons. Carnosine is now thought of as an intracellular pH buffer modulator, Zn/Cu ion chelator, antioxidant, aldehyde-scavenger, anti-glycating and anti-crosslinking agent for proteins. Furthermore, in the central nervous system, the CNS, it appears to work as a multi-functionally homeostatic and protective molecule in neuronal and non-neuronal cells. Taken together, carnosine appears to protect against neurodegenerative conditions.
Carnosine together with homocarnosine and anserine have been shown to act as scavengers of hydroxyl radicals (•OH). Aruoma et al. in 1989 suggested that carnosine and anserine may act as an antioxidant at physiological levels.
Barski et al. in 2013 reported that carnosine inhibits atherogenesis by facilitating aldehyde removal from atherosclerotic lesions. Carnosine prevents oxidation of low-density lipoprotein (LDL) as well as the cytotoxicity of reactive aldehydes generated by lipid oxidation.
In mice, dietary intake of carnosine decreases the formation of atherosclerotic lesions. However, the role of LDL oxidation in atherogenesis remains unclear. Barski et al. suggested that treatment with carnosine may decrease atherosclerosis by preventing LDL oxidation and the cytotoxic effects of lipid peroxidation products.
Atherogenesis is a disorder of the artery wall. Atherogenesis is characterized by the adhesion of monocytes, phagocytic white blood cells, lymphocytes, small white blood cells of the lymphatic system, to the endothelial cell surface, and the migration of monocytes into the sub-endothelial space, the differentiation into macrophages and the ingestion of low-density lipoproteins and modified or oxidized low-density lipoproteins by macrophages via several pathways. The result is an accumulation of cholesterol esters and the formation of “foam cells”. The foam cells together with T lymphocytes form the fatty streak. Migrating vascular smooth muscle cells into the intima proliferate and form the atherosclerotic plaques. The term intima refers to the innermost coating or membrane of a part or organ, in this case, a vain or artery.
All steps of this process involve cell adhesion, migration, differentiation, proliferation and cell interaction with the extracellular matrix which are regulated by a complex network or cascade of cytokines and growth regulatory peptides. Therefore it is thought that atherosclerosis is a result of a inflammatory-fibroproliferative process which has developed into a chronic disease state.
Also in 2013, Aloisi et al. reported that carnosine inhibits Aβ1-42 fibrillogenesis in vitro. Published results showed an effective role of carnosine against Aβ1-42 aggregation. The data suggest that carnosine induces a less ordered Aβ1-42 amyloid aggregation causing a lesser growth of fibrils. Carnosine appears to operate as an interfering, anti-aggregating agent. To date, small oligomers are considered the major aggressive variant of the amyloid formations. The so-called “oligomer cascade hypothesis” is a key premise in structure-neurotoxicity relationship studies of amyloid formations.
Alzheimer’s disease is the 3rd most costly disease and estimated to be the 6th leading cause of death. Researchers still search to identify the primary toxin that causes Alzheimer’s disease.
Aloisi, A., Barca, A., Romano, A., Guerrieri, S., Storelli, C., Rinaldi, R., & Verri, T. (2013). Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation. PLoS ONE, 8(7), e68159. http://doi.org/10.1371/journal.pone.0068159.
Aruoma, OI; Laughton, MJ; Halliwell, B (1989). "Carnosine, homocarnosine and anserine: could they act as antioxidants in vivo?". The Biochemical Journal. 264 (3): 863-9. doi:10.1042/bj2640863. PMC 1133665. PMID 2559719.
Bickford PC, Tan J, Shytle RD, Sanberg CD, El-Badri N, Sanberg PR.Nutraceuticals synergistically promote proliferation of human stem cells. Stem Cells Dev. 2006 Feb;15(1):118-23.
Ferreira, S. T., & Klein, W. L. (2011). The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s diseas. Neurobiology of Learning and Memory, 96(4), 529–543. http://doi.org/10.1016/j.nlm.2011.08.003
Gulewitsch, Wl.; Amiradžibi, S. (1900). "Ueber das Carnosin, eine neue organische Base des Fleischextractes". Berichte der deutschen chemischen Gesellschaft. 33 (2): 1902–1903. doi:10.1002/cber.19000330275.
Ross R, Agius L.; The process of atherogenesis--cellular and molecular interaction: from experimental animal models to humans. Diabetologia. 1992 Dec;35 Suppl 2:S34-40.
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