Principal Investigators

    Professor Oliver Bandmann


    University of Sheffield

    Contact information of lead PI


    United Kingdom

    Title of project or programme

    Glucocerebrosidase deficiency, alpha-synuclein and Parkinson's: A zebrafish study

    Source of funding information

    Parkinson's UK

    Total sum awarded (Euro)

    € 183,445

    Start date of award


    Total duration of award in years



    Research Abstract

    Background: Heterozygote mutations in the glucocerebrosidase 1 gene (GBA1+/-) are the most common genetic susceptibility factor for Parkinson’s disease (PD). Enzymatic glucocerebrosidase activity is also decreased in PD brains in the absence of a GBA1+/- mutation.
    However, only some GBA1+/-carriers develop PD and the precise mechanisms how partial glucocerebrosidase deficiency (PGD) leads to neuronal cell loss are only partially understood.
    Pilot data: We have established a stable mutant zebrafish (Danio rerio) line, carrying a 23 bp deletion in gba1, the zebrafish orthologue of human GBA1. Juvenile gba-/- zebrafish develop marked behavioural, morphological and biochemical abnormalities, all consistent with glucocerebrosidase deficiency. We have also generated stable alpha-synuclein transgenic zebrafish lines, overexpressing either wild-type (Tg( SNCAwt)) or E46K-mutant alpha-synuclein (Tg(SNCAE46K)).
    Objectives and methods: 1. To determine the effect of PGD on alpha-synuclein-related neurotoxicityin vivo (by crossing gba+/- with Tg(SNCAwt) or Tg(SNCAE46K); 2. To undertake an in vivo compound screen to identify drugs which upregulate enzymatic glucocerebrosidase activity in brain tissue (initial readout: effect of compounds on gba1 expression with subsequent validation experiments).
    Expected outcome: Better understanding of PGD-related mechanisms and identification of compounds enhancing glucocerebrosidase activity in brain tissue will hopefully lead to improved therapy for PD.

    Further information available at:

Types: Investments < €500k
Member States: United Kingdom
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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