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Gelsolin co-occurs with Lewy bodies in vivo and accelerates alpha-synuclein aggregation in vitro
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
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2011 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 412, no 1, 32-38 p.Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
2011. Vol. 412, no 1, 32-38 p.
Keyword [en]
alpha-Synuclein, Gelsolin, Lewy body, Dementia with Lewy bodies, Parkinson's disease, Aggregation
National Category
Medical and Health Sciences Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
URN: urn:nbn:se:uu:diva-158901DOI: 10.1016/j.bbrc.2011.07.027ISI: 000294509000006PubMedID: 21798243OAI: oai:DiVA.org:uu-158901DiVA: diva2:441783
Available from: 2011-09-19 Created: 2011-09-19 Last updated: 2017-12-08Bibliographically approved

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Welander, HedvigNäsström, TomasKarlsson, MikaelNikolajeff, FredrikLannfelt, LarsIngelsson, MartinBergström, Joakim

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