Protein/lipid coaggregates are formed during α-synuclein-induced disruption of lipid bilayers
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Protein/lipid coaggregates are formed during α-synuclein-induced disruption of lipid bilayers. / van Maarschalkerweerd, Andreas; Vetri, Valeria; Langkilde, Annette Eva; Foderà, Vito; Vestergaard, Bente.
I: Biomacromolecules, Bind 15, Nr. 10, 13.10.2014, s. 3643-54.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Protein/lipid coaggregates are formed during α-synuclein-induced disruption of lipid bilayers
AU - van Maarschalkerweerd, Andreas
AU - Vetri, Valeria
AU - Langkilde, Annette Eva
AU - Foderà, Vito
AU - Vestergaard, Bente
PY - 2014/10/13
Y1 - 2014/10/13
N2 - Amyloid formation is associated with neurodegenerative diseases such as Parkinson's disease (PD). Significant α-synuclein (αSN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including the molecular mechanisms behind potential amyloid-mediated toxic effects, is still missing. Interaction between amyloid aggregates and the lipid cell membrane is expected to play a key role in the disease progress. Here, we present experimental data based on hybrid analysis of two-photon-microscopy, solution small-angle X-ray scattering and circular dichroism data. Data show in real time changes in liposome morphology and stability upon protein addition and reveal that membrane disruption mediated by amyloidogenic αSN is associated with dehydration of anionic lipid membranes and stimulation of protein secondary structure. As a result of membrane fragmentation, soluble αSN:-lipid coaggregates are formed, hence, suggesting a novel molecular mechanism behind PD amyloid cytotoxicity.
AB - Amyloid formation is associated with neurodegenerative diseases such as Parkinson's disease (PD). Significant α-synuclein (αSN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including the molecular mechanisms behind potential amyloid-mediated toxic effects, is still missing. Interaction between amyloid aggregates and the lipid cell membrane is expected to play a key role in the disease progress. Here, we present experimental data based on hybrid analysis of two-photon-microscopy, solution small-angle X-ray scattering and circular dichroism data. Data show in real time changes in liposome morphology and stability upon protein addition and reveal that membrane disruption mediated by amyloidogenic αSN is associated with dehydration of anionic lipid membranes and stimulation of protein secondary structure. As a result of membrane fragmentation, soluble αSN:-lipid coaggregates are formed, hence, suggesting a novel molecular mechanism behind PD amyloid cytotoxicity.
U2 - 10.1021/bm500937p
DO - 10.1021/bm500937p
M3 - Journal article
C2 - 25210839
VL - 15
SP - 3643
EP - 3654
JO - Biomacromolecules
JF - Biomacromolecules
SN - 1525-7797
IS - 10
ER -
ID: 129662088