Owing to its poly-anionic charge and large hydrodynamic volume, polysialic acid (polySia) attached to neural cell adhesion molecule regulates axon–axon and axon–substratum interactions and signalling, particularly, in the development of the central nervous system (CNS). Expression of polySia is spatiotemporally regulated by the action of two polysialyl transferases, namely ST8SiaII and ST8SiaIV. PolySia expression peaks during late embryonic and early post-natal period and maintained at a steady state in adulthood in neurogenic niche of the brain. Aberrant polySia expression is associated with neurological disorders and brain tumours. Investigations on the structure and functions, over the past four decades, have shed light on the physiology of polySia. This review focuses on the biological, biochemical, and chemical tools available for polySia engineering. Genetic knockouts, endo-neuraminidases that cleave polySia, antibodies, exogenous expression, and neuroblastoma cells have provided deep insights into the ability of polySia to guide migration of neuronal precursors in neonatal brain development, neuronal clustering, axonal pathway guidance, and axonal targeting. Advent of metabolic sialic acid engineering using ManNAc analogues has enabled reversible and dose-dependent modulation polySia in vitro and ex vivo. In vivo, ManNAc analogues readily engineer the sialoglycans in peripheral tissues, but show no effect in the brain. A recently developed carbohydrate-neuroactive hybrid strategy enables a non-invasive access to the brain in living animals across the blood–brain barrier. A combination of recent advances in CNS drugs and imaging with ManNAc analogues for polySia modulation would pave novel avenues for understanding intricacies of brain development and tackling the challenges of neurological disorders.
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Cover Image
Cover Image
The lack of availability of glycans and glycoconjugates has severely limited the development of the field of glycobiology. This issue of Emerging Topics in Life Sciences features nine reviews by respected scientists in the field and deals with the application of metabolic engineering to the production of these complex carbohydrate or saccharide structures. The cover image illustrates that capsular polysaccharides and other bioengineered compounds can be generated by engineered cells, such as Escherichia coli, through the application of various metabolic engineering tools and strategies. The image was kindly provided by Robert J. Linhardt (Rensselaer Polytechnic Institute) and designed by Asher Williams (Rensselaer Polytechnic Institute).
Chemical and biological methods for probing the structure and functions of polysialic acids
Mattheos A.G. Koffas, Robert J. Linhardt, Surbhi Goswami, Shubham Parashar, Vandita Dwivedi, Asif Shajahan, Srinivasa-Gopalan Sampathkumar; Chemical and biological methods for probing the structure and functions of polysialic acids. Emerg Top Life Sci 26 October 2018; 2 (3): 363–376. doi: https://doi.org/10.1042/ETLS20180008
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