Disruptive membrane interactions of alpha-synuclein aggregates

Aditya Iyer, Mireille M. A. E. Claessens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)
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Abstract

Alpha synuclein (alpha S) is a similar to 14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on alpha Syet its physiological function remains largely elusive. The conversion of monomeric alpha S into oligomers and amyloid fibrils is believed to play a central role of the pathology of Parkinson's disease (PD). It is becoming increasingly clear that the interactions of alpha S with cellular membranes are important for both alpha S's functional and pathogenic actions. Therefore, understanding interactions of alpha S with membranes seems critical to uncover functional or pathological mechanisms. This review summarizes our current knowledge of how physicochemical properties of phospholipid membranes affect the binding and aggregation of alpha S species and gives an overview of how post-translational modifications and point mutations in alpha S affect phospholipid membrane binding and protein aggregation. We discuss the disruptive effects resulting from the interaction of alpha S aggregate species with membranes and highlight current approaches and hypotheses that seek to understand the pathogenic and/or protective role of alpha S in PD.

Original languageEnglish
Pages (from-to)468-482
Number of pages15
JournalBiochimica et biophysica acta-Proteins and proteomics
Volume1867
Issue number5
DOIs
Publication statusPublished - May-2019

Keywords

  • Alpha-synuclein
  • Membrane
  • Amyloid
  • Interactions
  • Aggregation
  • A-BETA COMPONENT
  • N-TERMINAL ACETYLATION
  • PARKINSONS-DISEASE
  • IN-VITRO
  • LEWY BODY
  • ALZHEIMERS-DISEASE
  • PRESYNAPTIC PROTEIN
  • OXIDATIVE STRESS
  • LIPID VESICLES
  • POSTTRANSLATIONAL MODIFICATIONS

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