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

• 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.

Nyckelord

alpha-Synuclein

Gelsolin

Lewy body

Dementia with Lewy bodies

Parkinson's disease

Aggregation

Teknisk fysik med inriktning mot mikrosystemteknik

Engineering Science with specialization in Microsystems Technology

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