RAGE Splicing Variants in Mammals

  • Katharina Anna Sterenczak
  • Ingo Nolte
  • Hugo Murua EscobarEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 963)


The receptor for advanced glycation end products (RAGE) is a multiligand receptor of environmental stressors which plays key roles in pathophysiological processes, including immune/inflammatory disorders, Alzheimer’s disease, diabetic arteriosclerosis, tumorigenesis, and metastasis. Besides the full-length RAGE protein in humans nearly 20 natural occurring RAGE splicing variants were described on mRNA and protein level. These naturally occurring isoforms are characterized by either N-terminally or C-terminally truncations and are discussed as possible regulators of the full-length RAGE receptor either by competitive ligand binding or by displacing the full-length protein in the membrane. Accordingly, expression deregulations of the naturally occurring isoforms were supposed to have significant effect on RAGE-mediated disorders. Thereby the soluble C-truncated RAGE isoforms present in plasma and tissues are the mostly focused isoforms in research and clinics. Deregulations of the circulating levels of soluble RAGE forms were reported in several RAGE-associated pathological disorders including for example atherosclerosis, diabetes, renal failure, Alzheimer’s disease, and several cancer types.

Regarding other mammalian species, the canine RAGE gene showed high similarities to the corresponding human structures indicating RAGE to be evolutionary highly conserved between both species. Similar to humans the canine RAGE showed a complex and extensive splicing activity leading to a manifold pattern of RAGE isoforms. Due to the similarities seen in several canine and human diseases—including cancer—comparative structural and functional analyses allow the development of RAGE and ligand-specific therapeutic approaches beneficial for human and veterinary medicine.

Key words

RAGE Isoforms Mammalian variants Comparative genetics Receptor for advanced glycation end products 


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Katharina Anna Sterenczak
    • 1
  • Ingo Nolte
    • 1
  • Hugo Murua Escobar
    • 2
    Email author
  1. 1.Small Animal ClinicUniversity for Veterinary MedicineHannoverGermany
  2. 2.Small Animal ClinicUniversity of Veterinary MedicineHannoverGermany

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