Gelsolin co-occurs with Lewy bodies in vivo and accelerates b1;-synuclein aggregation in vitro

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• 作者：Hedvig Welander^a ; Sai Vineela Bontha^a ; Thomas Nä ; sstr&#xf6 ; m^a ; Mikael Karlsson^b ; Fredrik Nikolajeff^b ; Karin Danzer^c ; ^d ; Marcus Kostka^c ; Hannu Kalimo^e ; Lars Lannfelt^a ; Martin Ingelsson^a ; Joakim Bergstr&#xf6 ; m^a ; ^{joakim.bergstrom@pubcare.uu.se" rel="nofollow}
• 关键词：b1 ; -Synuclein ; Gelsolin ; Lewy body ; Dementia with Lewy bodies ; Parkinson’ ; s disease ; Aggregation
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：19 August 2011
• 年：2011
• 卷：412
• 期：1
• 页码：32-38
• 全文大小：1533 K
• ISSN：S0006291X11012460

文摘

Deposition of fibrillar b1;-synuclein as Lewy bodies is the neuropathological hallmark of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Apart from b1;-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 b1;-synuclein aggregation remains unknown. Here, we studied the association between gelsolin and b1;-synuclein in brain tissue from PD and DLB patients as well as in a cell model for b1;-synuclein aggregation. Moreover, the potential effect of gelsolin on b1;-synuclein fibrillization was also investigated. Our data demonstrate that gelsolin co-occured with b1;-synuclein in Lewy bodies from affected human brain as well as with Lewy body-like inclusions in b1;-synuclein over expressing cells. Furthermore, in the presence of calcium chloride, gelsolin was found to enhance the aggregation rate of b1;-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 b1;-synuclein aggregation process.