Viable Neuronopathic Gaucher Disease Model in Medaka () Displays Axonal Accumulation of Alpha-Synuclein

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Parkinson’s disease (PD) is a neurodegenerative disease characterized by intraneuronal accumulation of alpha-synuclein (α-syn) called Lewy bodies and Lewy neurites. Recent genetic studies have revealed that mutations in glucocerebrosidase (GBA), a causative gene of Gaucher disease (GD), are a strong risk for PD. However, its pathological mechanisms leading to PD remain largely unknown. Here, we generated GBA nonsense mutant (GBA-/-) medaka which survive long enough for pathological analysis of disease progression. These mutant medaka display not only the phenotypes resembling human neuronopathic GD but also axonal accumulation of α-syn accompanied by impairment of the autophagy-lysosome pathway. Furthermore, the present study demonstrates this α-syn accumulation has negligible contribution to the pathogenesis of neuronopathic GD in medaka. GBA-/- medaka represent a valuable model for exploring the pathological mechanisms of PD with GBA mutations as well as neuronopathic GD, and our findings have important implications for the association of GBA mutations with PD.

Vyšlo v časopise: Viable Neuronopathic Gaucher Disease Model in Medaka () Displays Axonal Accumulation of Alpha-Synuclein. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005065
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005065

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