Abstract
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.
Highlights
Parkinson disease (PD) is the most common neurodegenerative movement disorder, estimated to affect 4% of individuals over 80 years of age [1]
Prominent accumulation of p-αSYN was observed in the striatum, layer 2 of the motor cortex, layer 5 of the cingulate cortex and in the substantia nigra pars compacta (SNpc) (Figs 1C, 2A–2C and S1C and S2A–S2C)
We showed that GCase deficiency greatly increases formation of pathological p-αSYN deposits in transgenic mice following αSYN-PFF injection
Summary
Parkinson disease (PD) is the most common neurodegenerative movement disorder, estimated to affect 4% of individuals over 80 years of age [1]. The most common risk factor for PD are mutations in the glucocerebrosidase 1 (GBA1) gene, which encodes an enzyme (GCase) that is involved in glycolipid metabolism. It has been estimated that at least 7–10% of non-Ashkenazi PD individuals have a GBA1 mutation (PD-GBA1) [2]. The molecular mechanisms by which GBA1 mutations increase PD risk are still unclear, it is likely that α-synuclein accumulation plays an important role. The link between GCase deficiency, α-synuclein accumulation and neurodegeneration in the substantia nigra has recently been explored in a heterozygous Gba mouse model carrying.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
