Abstract:
BACKGROUND:Pregnancy specific β1-glycoproteins (PSGs) have long been recognized as trophoblast quality and embryo viability markers. However, biological roles of PSGs remain obscure, and structure/function relationships to other feto-placental proteins as well as implications for drug design have not been reviewed. This review summarizes and discusses advances in 45-year studies of PSGs with focus on the latest achievements and the challenges for future investigations. METHODS:Literature search was performed to review the majority of recent PSG studies with emphasis on usage of high-throughput integrated proteomic profiling technologies, systems biology and bioinformatics approaches that enhance novel biomarker and drug target discovery as well as protein structure/activity analysis. RESULTS:Clinical significance and screening performance improved when PSG measurements were combined with those of other placenta-derived proteins: hCG, hPL, PAPP-A, and proMBP. Nevertheless, analysis of protein co-expression and co-localization data and the involvement of PSGs in protein interaction networks are being introduced to discover novel, specific and high-sensitive, gestational/cancer biomarkers. Despite biological roles of PSGs are not fully understood, there are evidences of that they exhibit immunomodulatory, antiinflammatory and proangiogenic effects. Investigation of structure/function relationships showed that PSGs may function in cooperative/coordinated manner with numerous regulatory proteins including alpha-fetoprotein and transforming growth factors-β; this is provided by the presence of conserved short linear motifs (SLiMs) such as RGD, PXXP and AFP14-20-like (YXCX) ones. CONCLUSION:PSG-derived peptides may be used as a rationale to design novel drugs that mimic SLiMs involved in protein-protein interactions to inhibit domain-motif binding and to block cell signaling, and/or exert immunomodulatory, anti-inflammatory and proangiogenic effects.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Moldogazieva NT,Mokhosoev IM,Terentiev AAdoi
10.2174/0929867324666161123090554subject
Has Abstractpub_date
2017-01-01 00:00:00pages
245-267issue
3eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-79886journal_volume
24pub_type
杂志文章,评审abstract::A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have incr...
journal_title:Current medicinal chemistry
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