Abstract
Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders.
Highlights
Imidazole dipeptides (ID) in biological tissuesThe mammalian essential amino acid L-histidine originates compounds in biological tissues, including histamine [1], and the ID carnosine, homocarnosine, and anserine [2]
Liquid chromatography/electrospray ionization tandem mass spectrometry analyses performed in plasma or tissue homogenates from rats showed that the highest concentrations of carnosine and anserine are found in skeletal muscles, heart and brain
Homocarnosine is present in human central nervous system (CNS) and is synthesized in specific GABAergic neurons [4,5]
Summary
The mammalian essential amino acid L-histidine originates compounds in biological tissues, including histamine [1], and the ID carnosine, homocarnosine, and anserine [2]. Carnosine biosynthesis from its precursor amino acids is catalyzed by carnosine synthase coupled to ATP hydrolysis [2] It occurs in excitable tissues, such as skeletal muscle cells [15] and oligodendrocytes [16]. Other dipeptidase able to cleave carnosine in biological tissues is the cytosol nonspecific dipeptidase (CNDP, EC 3.4.13.18) This protein is constitutively expressed in brain, kidneys, liver, spleen, gonads, lungs, and pancreas [17]. Li and co-workers [27] showed that the number of lymphocytes in spleen and the level of plasma corticosterone presented no significant alterations in stressed animals receiving carnosine previously The administration of this peptide elicited antidepressant-like effects in rats subjected to forced swimming [28]. The present review gather information regarding the current state of ID utilization as drug therapy for age-related human disorders in clinical trials, as well as their safety
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