Amyloid oligomerization of the Parkinson's disease related protein α-synuclein impacts on its curvature-membrane sensitivity

GALLEA, J. IGNACIO; AMBROGGIO, ERNESTO E.; VILCAES, A. ALEJANDRO; JAMES, NICHOLAS G.; JAMESON, DAVID M.; CELEJ, M. SOLEDAD

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2018

0022-3042

he amyloid aggregation of the presynaptic protein α‐synuclein (AS) is pathognomonic of Parkinson's disease and other neurodegenerative disorders. Physiologically, AS contributes to synaptic homeostasis by participating in vesicle maintenance, trafficking and release. Its avidity for highly curved acidic membranes has been related to the distinct chemistry of the N‐terminal amphipathic helix adopted upon binding to appropriated lipid interfaces. Pathologically, AS populate a myriad of toxic aggregates ranging from soluble oligomers to insoluble amyloid fibrils. Different gain‐of‐toxic function mechanisms are linked to prefibrillar oligomers which are considered as the most neurotoxic species. Here, we investigated if amyloid oligomerization could hamper AS function as a membrane curvature sensor. We used fluorescence correlation spectroscopy to quantitatively evaluate the interaction of oligomeric species, produced using a popular method based on lyophiliza