Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part I: Helminths

Cysteine proteinase (CP) is a new era as well as interesting topic in several publications during the last two decades. CPs enable several different biological activities in parasite biology and pathogenesis such as digestion of host proteins for nutrition, invasion through cellular and tissue barriers, processing secondary protein modifications for parasite survival as well as manipulation of the host immune system (iininunomodulation). In this regard, CPs, like heat shock proteins, are suggested to be virulence factors and serodiagnostic markers. Therefore, CPs data are utilized as drug targets or vaccine candidates through use of their inhibitors as well as in diagnosis of several parasitic diseases. MEROPS is an on-line database for classification, characterization and structural properties of all identified proteinases and their inhibitors. Parasites express not only proteolytic enzymes for their survival and long persistence, but also inhibitors; cystatins, serpins and aspins to inhibit cysteine, serine and aspartic proteinases, respectively, both of the host and their own. On the other hand, CPs inhibitors (CPIs) are either general, inhibiting members of all classes of proteinases, or specific; inhibiting only one class of proteinases. However, a new classification was adopted in 2007, according to their structure; either with low molecular weight peptidomimetic inhibitors or those composed of one or more peptide chains. In spite of that, the majority of research studies used the old classification, general and specific CPIs. The main objective of the this review is to present updated data for all identified CPs and CYSs expressed in helminths and use of their CPIs as chemotherapeutic drug targets or as protective vaccine candidates. The secondary objective is to simplify, as possible, new approaches for drug and vaccine development as well as accurate diagnostic methods in parasitological researches utilizing the terrible evolution in bioinformatics and technology.