The Serum Amyloid A (SAA) Family: (Patho)Physiological Functions in (Non)Mammalian Systems

Dear Colleagues,

The Serum Amyloid A (SAA) family is commonly considered an evolutionary old and highly conserved family consisting of basically four different proteins (SAA1–SAA4) encoded by four different genes (SAA1–SAA4 or Saa1–Saa4) in the mammalian system. SAA1 and SAA2 (commonly termed acute-phase SAA [A-SAA]) share high homology on DNA/RNA (including various allelic variations) and on a protein level, which were originally considered to be only of hepatic origin. From a classical point of view, their major functions were previously considered to be as follows: (i) as precursor proteins of secondary reactive amyloidosis (forming amyloid fibrils), (ii) as classical acute-phase reactants, and (iii) as major protein moiety of high-density lipoproteins during inflammation. However, ongoing studies have revealed the extrahepatic expression of non-glycosylated A-SAA proteins, which may act locally and serve as potential biomarkers in chronic diseases, including different types of cancer, chronic obstructive pulmonary disease, atherosclerosis, innate immunity, and others.

Despite the fact that, in humans, SAA3 has been definitively confirmed to be a pseudogene, while SAA3 proteins of other mammalian species may well be considered as potent acute-phase reactants with yet widely unidentified functions. In particular, sexually dimorphic relationships among Saa3, inflammation, and cholesterol metabolism have been reported to modulate atherosclerosis in the murine system.

In contrast to mammalian SAA1/2 proteins, glycosylated SAA4 (which, in principle, is not prone to form amyloid A fibrils) is not considered a major acute-phase reactant. Therefore, it is termed as constitutively expressed SAA [C-SAA], although it shares striking homology with SAA1/2 in the N-terminal portion. SAA4 is abundantly expressed in humans and mice, although its function is largely unknown. Surprisingly, rats, the only mammalian species thus far that has been identified to not express A-SAA on a protein level, are prone to expressing SAA4.

Therefore, the main focus of this Special Issue will be the expression and roles of different (non)mammalian SAA1–4 mRNAs and proteins in (patho)physiological conditions, their potential activities in promoting disease progression, and their use as potential targets for therapy. In particular, clinical studies, as well as preclinical models with SAA-knock-out, double knock-out or even knock-in models, should be considered to shed light on the adverse or beneficial effects of SAA both in human pathologies and other (non)mammalian species.

We cordially invite you to contribute to this Special Issue with original research articles, brief communications, or specific overviews on SAA-related topics and comparison of SAA with other potential acute-phase reactants.

Thank you very much in advance for your consideration, and we sincerely hope to welcome you as a contributor to our Special Issue on SAA.

Prof. Dr. Ernst Malle
Prof. Dr. János G. Filep
Guest Editors

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