Molecular Neurobiology

, Volume 47, Issue 2, pp 525–536

Recent Advances in α-Synuclein Functions, Advanced Glycation, and Toxicity: Implications for Parkinson’s Disease

  • Erika Guerrero
  • P. Vasudevaraju
  • Muralidhar L. Hegde
  • G. B. Britton
  • K. S. Rao
Article

DOI: 10.1007/s12035-012-8328-z

Cite this article as:
Guerrero, E., Vasudevaraju, P., Hegde, M.L. et al. Mol Neurobiol (2013) 47: 525. doi:10.1007/s12035-012-8328-z

Abstract

The toxicity of α-synuclein in the neuropathology of Parkinson’s disease which includes its hallmark aggregation has been studied scrupulously in the last decade. Although little is known regarding the normal functions of α-synuclein, its association with membrane phospholipids suggests its potential role in signaling pathways. Following extensive evidences for its nuclear localization, we and others recently demonstrated DNA binding activity of α-synuclein that modulates its conformation as well as aggregation properties. Furthermore, we also underscored the similarities among various amyloidogenic proteins involved in neurodegenerative diseases including amyloid beta peptides and tau. Our more recent studies show that α-synuclein is glycated and glycosylated both in vitro and in neurons, significantly affecting its folding, oligomeric, and DNA binding properties. Glycated α-synuclein causes increased genome damage both via its direct interaction with DNA and by increased generation of reactive oxygen species as glycation byproduct. In this review, we discuss the mechanisms of glycation and other posttranslational modifications of α-synuclein, including phosphorylation and nitration, and their role in neuronal death in Parkinson’s disease.

Keywords

α-Syn AGEs Lewy body Neurodegeneration PD 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Erika Guerrero
    • 1
    • 4
  • P. Vasudevaraju
    • 2
  • Muralidhar L. Hegde
    • 3
  • G. B. Britton
    • 1
  • K. S. Rao
    • 1
  1. 1.Centre for Neuroscience, Institute for Scientific Research and Technological Services (INDICASAT-AIP)City of KnowledgePanamaRepublic of Panama
  2. 2.Department of NeuroscienceMedical University of South CarolinaCharlestonUSA
  3. 3.Department of Biochemistry and Molecular BiologyUniversity of Texas Medical BranchGalvestonUSA
  4. 4.Department of BiotechnologyAcharya Nagarjuna UniversityGunturIndia

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