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Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO4 and SiO4 that generates cavities where water and other polar molecules or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). ZC is an excellent detoxifying, antioxidant and anti-inflammatory agent. As a result, it is been used in many industrial applications ranging from environmental remediation to oral applications/supplementation in vivo in humans as food supplements or medical devices. Moreover, the modification as micronization of ZC (M-ZC) or tribomechanically activated zeolite clinoptilolite (TMAZ) or furthermore as double tribomechanically activated zeolite clinoptilolite (PMA-ZC) allows improving its benefits in preclinical and clinical models. Despite its extensive use, many underlying action mechanisms of ZC in its natural or modified forms are still unclear, especially in humans. The main aim of this review is to shed light on the geochemical aspects and therapeutic potentials of ZC with a vision of endorsing further preclinical and clinical research on zeolites, in specific on the ZC and its modified forms as a potential agent for promoting human brain health and overall well-being.

The human salivary acidic proline-rich proteins (aPRPs) complex was investigated by different chromatographic and mass spectrometric approaches and the main aPRPs, namely PRP-1, PRP-2 and PIF-s (15,515 amu), Db-s (17,632 amu) and Pa (15,462 amu) proteins, were detected. All these isoforms are phosphorylated at Ser-8 and Ser-22 and have a pyroglutamic moiety at the N-terminus. Apart from Pa, all the other aPRPs undergo a proteolytic cleavage at Arg-106 residue (Arg-127 in Db-s protein), that generates the small PC peptide (4371 amu) and PRP-3, PRP-4, PIF-f (11,162 amu) and Db-f (13,280 amu) proteins, all of which were detected. With regard to the Pa protein, the main form detected was the dimeric derivative (Pa 2-mer, 30,922 amu) originated by a disulfide bond involving Cys-103 residue. Besides these known isoforms, several previously undetected aPRP derivatives were found (in minor amounts): (i) the triphosphorylated derivatives of PRP-1/PRP-2/PIF-s and Db-s, showing the additional phosphate group at Ser-17; (ii) the mono-phosphorylated forms at either Ser-22 or Ser-8 of PRP-1/PRP-2/PIF-s, PRP-3/PRP-4/PIF-f, Db-s and Db-f; (iii) a nonphosphorylated form of PRP-3/PRP-4/PIF-f; (iv) the triphosphorylated and diphosphorylated forms of Pa 2-mer. Moreover, minor quantities of PRP-3/PRP-4/PIF-f lacking the C-terminal Arg (11,006 amu), and of Pa 2-mer lacking the C-terminal Gln (30,793 amu) were found. By this approach the different phenotypes of PRH1 locus in 59 different subjects were characterized.

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