Lecture: Molecular factors responsible for the modulation of the lipid-induced aggregation of alpha-synuclein

06.03.2017, 11:00

Dr. Céline Galvagnion, Institute of Physical Biology, Heinrich-Heine-Universität Düsseldorf

Time, place:

Monday, 6th March 2017, 11:00h

Seminar Room A1.500, MPL, Staudtstr. 2, 91058 Erlangen


The conversion of soluble monomeric a-synuclein into amyloid fibrils is the hallmark of a range of neurological disorders, including Parkinson’s disease. Unlike other amyloidogenic proteins, such as Ab peptide, involved in Alzheimer’s disease, a-synuclein is surprisingly stable in solution under quiescent conditions and its aggregation is mainly triggered via interaction with surfaces including air/water interface, surfactants, lipid membranes. In fact, we have recently shown that negatively charged lipid vesicles can trigger the aggregation of a-synuclein by enhancing the rate of primary nucleation by up to 3 orders of magnitude (1). In addition, our results indicate that both the protein:lipid ratio (1) and the chemical properties of the lipids play a role in modulating the kinetics of a-synuclein lipid-induced aggregation (2). Finally, we have shown that both intrinsic (disease associated mutations) and extrinsic (homologous proteins and small molecules) factors can modulate the lipid-induced aggregation of a-synuclein by perturbing its binding to the membrane (3-5). These findings are essential for elucidating the molecular determinants responsible for the switch between functional and deleterious interactions between a-synuclein and membranes.  


1.       Galvagnion C, Buell AK, Meisl G, Michaels TC, Vendruscolo M, Knowles TP, Dobson CM. Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation. Nat Chem Biol. 2015 Mar;11(3):229-34.

2.       Galvagnion C, Brown JW, Ouberai MM, Flagmeier P, Vendruscolo M, Buell AK, Sparr E, Dobson CM. Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7065-70.

3.       Flagmeier P, Meisl G, Vendruscolo M, Knowles TP, Dobson CM, Buell AK, Galvagnion C. Mutations associated with familial Parkinson's disease alter the initiation and amplification steps of α-synuclein aggregation. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):10328-33.

4.       Brown JW, Buell AK, Michaels TC, Meisl G, Carozza J, Flagmeier P, Vendruscolo M, Knowles TP, Dobson CM, Galvagnion C. β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces. Sci Rep. 2016 Nov 3;6:36010.

5.       Perni M, Galvagnion C, Maltsev A, Meisl G, Müller MB, Challa PK, Kirkegaard JB, Flagmeier P, Cohen SI, Cascella R, Chen SW, Limboker R, Sormanni P, Heller GT, Aprile FA, Cremades N, Cecchi C, Chiti F, Nollen EA, Knowles TP, Vendruscolo M, Bax A, Zasloff M, Dobson CM. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity. Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):E1009-E1017.