Sialic acids in human health and disease

Abstract

The surfaces of all vertebrate cells are decorated with a dense and complex array of sugar chains, which are mostly attached to proteins and lipids. Most soluble secreted proteins are also similarly decorated with such glycans. Sialic acids are a diverse family of sugar units with a nine-carbon backbone that are typically found attached to the outermost ends of these chains. Given their location and ubiquitous distribution, sialic acids can mediate or modulate a wide variety of physiological and pathological processes. This review considers some examples of their established and newly emerging roles in aspects of human physiology and disease.

Figure 1

Some biological and pathological roles of sialic acids. First, due to their negative charge and hydrophilicity, sialic acids have many structural or physical roles, for example in neural plasticity, glomerular filtration or blood cell charge repulsion. Second, sialic acids serve as components of binding sites for various pathogens and toxins [6,7,9,10], such as those listed in Table 1. In most such interactions, a pathogen-binding protein (extrinsic receptor) recognizes certain forms of sialic acids presented in specific linkages to a defined underlying sugar chain. In the case of recognition by extrinsic receptors (pathogen-binding proteins and toxins), only a few examples are listed. Third, sialic acids serve as ligands for intrinsic receptors such as Siglecs and factor H [8,10,12,90,96,97]. The possible interactions between sialic acids (as sialylated glycan molecules) expressed on host cells (self) with intrinsic receptors expressed on the same or different host cells is shown. A final class of functions is ‘molecular mimicry’, in which successful microbial pathogens decorate themselves with sialic acids, assisting in evasion of host immunity [11] (Table 2). These varied functions of sialic acids are to some extent antagonistic, generating an evolutionary arms race in which vertebrate hosts need to maintain sialic acids for critical endogenous functions – even while constantly changing them to avoid rapidly evolving pathogens that are either binding to or mimicking them [12]. Abbreviations: L1CAM, L1 cell adhesion molecule; PILR, paired immunoglobulin-like receptor.