Disruptive membrane interactions of alpha-synuclein aggregates

Aditya Iyer, Mireille M.A.E. Claessens* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
67 Downloads (Pure)

Abstract

Alpha synuclein (αS) is a ~14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on αS yet its physiological function remains largely elusive. The conversion of monomeric αS 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 αS with cellular membranes are important for both αS's functional and pathogenic actions. Therefore, understanding interactions of αS 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 αS species and gives an overview of how post-translational modifications and point mutations in αS affect phospholipid membrane binding and protein aggregation. We discuss the disruptive effects resulting from the interaction of αS aggregate species with membranes and highlight current approaches and hypotheses that seek to understand the pathogenic and/or protective role of αS 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 - 1 May 2019

Fingerprint

alpha-Synuclein
Membranes
Parkinson Disease
Phospholipids
Intrinsically Disordered Proteins
Agglomeration
Post Translational Protein Processing
Point Mutation
Amyloid
Pathology
Carrier Proteins
Membrane Proteins
Oligomers
Research

Keywords

  • UT-Hybrid-D
  • Alpha-synuclein
  • Amyloid
  • Interactions
  • Membrane
  • Aggregation

Cite this

@article{ec7b682e45464e9b9cd570d24d25cd4d,
title = "Disruptive membrane interactions of alpha-synuclein aggregates",
abstract = "Alpha synuclein (αS) is a ~14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on αS yet its physiological function remains largely elusive. The conversion of monomeric αS 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 αS with cellular membranes are important for both αS's functional and pathogenic actions. Therefore, understanding interactions of αS 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 αS species and gives an overview of how post-translational modifications and point mutations in αS affect phospholipid membrane binding and protein aggregation. We discuss the disruptive effects resulting from the interaction of αS aggregate species with membranes and highlight current approaches and hypotheses that seek to understand the pathogenic and/or protective role of αS in PD.",
keywords = "UT-Hybrid-D, Alpha-synuclein, Amyloid, Interactions, Membrane, Aggregation",
author = "Aditya Iyer and Claessens, {Mireille M.A.E.}",
note = "Elsevier deal",
year = "2019",
month = "5",
day = "1",
doi = "10.1016/j.bbapap.2018.10.006",
language = "English",
volume = "1867",
pages = "468--482",
journal = "Biochimica et biophysica acta : proteins and proteomics",
issn = "1570-9639",
publisher = "Elsevier",
number = "5",

}

Disruptive membrane interactions of alpha-synuclein aggregates. / Iyer, Aditya; Claessens, Mireille M.A.E. (Corresponding Author).

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1867, No. 5, 01.05.2019, p. 468-482.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Disruptive membrane interactions of alpha-synuclein aggregates

AU - Iyer, Aditya

AU - Claessens, Mireille M.A.E.

N1 - Elsevier deal

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Alpha synuclein (αS) is a ~14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on αS yet its physiological function remains largely elusive. The conversion of monomeric αS 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 αS with cellular membranes are important for both αS's functional and pathogenic actions. Therefore, understanding interactions of αS 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 αS species and gives an overview of how post-translational modifications and point mutations in αS affect phospholipid membrane binding and protein aggregation. We discuss the disruptive effects resulting from the interaction of αS aggregate species with membranes and highlight current approaches and hypotheses that seek to understand the pathogenic and/or protective role of αS in PD.

AB - Alpha synuclein (αS) is a ~14 kDa intrinsically disordered protein. Decades of research have increased our knowledge on αS yet its physiological function remains largely elusive. The conversion of monomeric αS 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 αS with cellular membranes are important for both αS's functional and pathogenic actions. Therefore, understanding interactions of αS 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 αS species and gives an overview of how post-translational modifications and point mutations in αS affect phospholipid membrane binding and protein aggregation. We discuss the disruptive effects resulting from the interaction of αS aggregate species with membranes and highlight current approaches and hypotheses that seek to understand the pathogenic and/or protective role of αS in PD.

KW - UT-Hybrid-D

KW - Alpha-synuclein

KW - Amyloid

KW - Interactions

KW - Membrane

KW - Aggregation

UR - http://www.scopus.com/inward/record.url?scp=85055100258&partnerID=8YFLogxK

U2 - 10.1016/j.bbapap.2018.10.006

DO - 10.1016/j.bbapap.2018.10.006

M3 - Article

AN - SCOPUS:85055100258

VL - 1867

SP - 468

EP - 482

JO - Biochimica et biophysica acta : proteins and proteomics

JF - Biochimica et biophysica acta : proteins and proteomics

SN - 1570-9639

IS - 5

ER -