title: Gelsolin co-occurs with Lewy bodies in vivo and accelerates α-synuclein aggregation in vitro.
abstract: Deposition of fibrillar α-synuclein as Lewy bodies is the neuropathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Apart from α-synuclein, these intraneuronal inclusions contain over 250 different proteins. The actin binding protein gelsolin, has previously been suggested to be part of the Lewy body, but its potential role in α-synuclein aggregation remains unknown. Here, we studied the association between gelsolin and α-synuclein in brain tissue from PD and DLB patients as well as in a cell model for α-synuclein aggregation. Moreover, the potential effect of gelsolin on α-synuclein fibrillization was also investigated. Our data demonstrate that gelsolin co-occured with α-synuclein in Lewy bodies from affected human brain as well as with Lewy body-like inclusions in α-synuclein over expressing cells. Furthermore, in the presence of calcium chloride, gelsolin was found to enhance the aggregation rate of α-synuclein in vitro. Moreover, no apparent structural differences could be observed between fibrils formed in the presence or absence of gelsolin. Further studies on gelsolin and other Lewy body associated proteins are warranted to learn more about their potential role in the α-synuclein aggregation process.
authors.affiliation: Department of Public Health/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Hedvig
authors.initials: H
authors.lastname: Welander
authors.forename: Sai Vineela
authors.initials: SV
authors.lastname: Bontha
authors.forename: Thomas
authors.initials: T
authors.lastname: Näsström
authors.forename: Mikael
authors.initials: M
authors.lastname: Karlsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nikolajeff
authors.forename: Karin
authors.initials: K
authors.lastname: Danzer
authors.forename: Marcus
authors.initials: M
authors.lastname: Kostka
authors.forename: Hannu
authors.initials: H
authors.lastname: Kalimo
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.forename: Joakim
authors.initials: J
authors.lastname: Bergström
mesh_terms: D000368:Aged; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018260:Gelsolin / Q000378:metabolism*; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism*; D008297:Male; D010300:Parkinson Disease / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D018260:Gelsolin; D051844:alpha-Synuclein; D002118:Calcium