Journal Article

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

Verona, Guglielmo, Migdalska‐Richards, Anna, Schapira, Anthony H. V., Bellotti, Vittorio, Wegrzynowicz, Michal, Harrison, Ian F., Spillantini, Maria Grazia

2020

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Accumulation / alpha-Synuclein - chemistry / alpha-Synuclein - metabolism / Amygdala / 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