Recent studies on the roles of antiglycosphingolipids in the pathogenesis of neurological disorders

Toshio Ariga, Tadashi Miyatake, Robert K. Yu

Research output: Contribution to journalShort surveypeer-review

29 Scopus citations

Abstract

Evidence is mounting to suggest a causal role of humoral immunity arising from antiglycosphingolipid (GSL) antibodies in a variety of neurological disorders. These disorders include the demyelinating and axonal forms of Guillain-Barre syndrome, multifocal motor neuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and IgM paraproteinemia. Many claims have been made regarding other neurological disorders, which should be carefully scrutinized for their validity, based on several criteria proposed in this review. These criteria include 1) characterization of the causative antigens and immunoglobulins, 2) correlation of the pathological lesions and clinical manifestation of the antigens, 3) establishment of animal models using pure GSLs as the antigens, 4) immunopathogenic mechanisms of the neurodenerative process, 5) mechanisms for the malfunctioning of blood-nerve barrier and the ensuing leakage of circulating antibodies into peripheral nerve parenchyma, and 6) the roles of anti-GSL antibodies that may cause humorally mediated nerve dysfunction and injury as well as interference with ion channel function at the node of Ranvier, where carbohydrate epitopes are located. Finally, the origin of the anti-GSL antibodies is discussed in light of the recent circumstantial evidence pointing to a molecular mimicry mechanism with infectious agents. With a better understanding of the immunopathogenic mechanisms, it will then be possible to devise rational and effective diagnostic and therapeutic strategies for the treatment of these neurological disorders.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalJournal of Neuroscience Research
Volume65
Issue number5
DOIs
StatePublished - Sep 1 2001

Keywords

  • Antibodies
  • Blood-nerve barrier
  • Demyelination
  • Ganglioside
  • Glycosphingolipid
  • Neurological diseases
  • Periperal neuropathy

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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