L444P Gba1 mutation increases formation and spread of α-synuclein deposits in mice injected with mouse α-synuclein pre-formed fibrils

Parkinson disease is the most common neurodegenerative movement disorder, estimated to affect one in twenty-five individuals over the age of 80. Mutations in glucocerebrosidase 1 (GBA1) represent the most common genetic risk factor for Parkinson disease. The link between GBA1 mutations and α-synucle...

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Bibliographic Details
Published in:PloS one 2020-08, Vol.15 (8), p.e0238075-e0238075
Main Authors: Migdalska-Richards, Anna, Wegrzynowicz, Michal, Harrison, Ian F, Verona, Guglielmo, Bellotti, Vittorio, Spillantini, Maria Grazia, Schapira, Anthony H V
Format: Article
Language:English
Subjects:
Accumulation
alpha-Synuclein - chemistry
alpha-Synuclein - metabolism
Animals
Biology and Life Sciences
Brain
Engineering and Technology
Fibrils
Gene Knock-In Techniques
Glucosylceramidase
Glucosylceramidase - genetics
Health risks
Humans
Inclusions
Injections
Laboratories
Medicine and Health Sciences
Mice
Movement disorders
Mutation
Neostriatum
Neostriatum - metabolism
Neurodegeneration
Neurodegenerative diseases
Neurosciences
Parkinson's disease
Pathology
Protein Aggregates - genetics
Research and Analysis Methods
Risk analysis
Risk factors
Synuclein
Transgenic mice
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Summary:Parkinson disease is the most common neurodegenerative movement disorder, estimated to affect one in twenty-five individuals over the age of 80. Mutations in glucocerebrosidase 1 (GBA1) represent the most common genetic risk factor for Parkinson disease. The link between GBA1 mutations and α-synuclein accumulation, a hallmark of Parkinson disease, is not fully understood. Following our recent finding that Gba1 mutations lead to increased α-synuclein accumulation in mice, we have studied the effects of a single injection of mouse α-synuclein pre-formed fibrils into the striatum of Gba1 mice that carry a L444P knock-in mutation. We found significantly greater formation and spread of α-synuclein inclusions in Gba1-transgenic mice compared to wild-type controls. This indicates that the Gba1 L444P mutation accelerates α-synuclein pathology and spread.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0238075