title: High pressure promotes alpha-synuclein aggregation in cultured neuronal cells.
abstract: α-Synuclein is found in plaques associated with Parkinson's and other neurodegenerative diseases. Changes in α-synuclein oligomerization are thought to give rise to nucleation of neurodegenerative plaques. Here, we investigated the effect of hydrostatic pressure on the aggregation of α-synuclein in cultured neuronal cells. We found that hydrostatic pressure is associated with a transition from monomeric to higher order α-synuclein aggregates. We then tested whether this aggregation is associated with the loss of binding partners, such as phospholipase Cβ. We found that increased pressure reduces the level of PLCβ1 and the amount of α-synuclein/PLCβ1 complexes. These studies suggest that pressure promotes release of α-synuclein from protein partners promoting its oligomerization.
authors.affiliation: Dept. of Biological Sciences and Geology, Queensborough Community College, Bayside, NY 11364, USA.
authors.forename: Urszula
authors.initials: U
authors.lastname: Golebiewska
authors.affiliation: Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA 01609 USA. Electronic address: sfscarlata@wpi.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D006874:Hydrostatic Pressure; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D054799:Phospholipase C beta / Q000378:metabolism*; D066329:Protein Aggregates; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D051381:Rats; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; C497604:SNCA protein, human; C497606:Snca protein, rat; D051844:alpha-Synuclein; D054799:Phospholipase C beta
keywords: Aggregation; Alpha synuclein; Hydrostatic pressure; Parkinson’s disease; Phospholipase beta 1