ArticleNPJ Parkinson's disease2024
Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase.
Article in NPJ Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- PPARγ Signaling in the Central Nervous System: A Review of the Implications in Synaptic Plasticity, Neuroinflammatory and Neoplastic Processes.Neurochemical research · 2026Review
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Isoorientin inhibits oxidative stress to ameliorate cognitive dysfunction in type 2 diabetes mice via GSK3β/Nrf2 axis.Metabolic brain disease · 2026Article
- Circadian gatekeepers of the gut-brain-immune axis: implications for neuroinflammation and neurodegeneration.Journal of neuroinflammation · 2026Review
- Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review.Current issues in molecular biology · 2026Review
- Selective peroxynitrite-mediated protein nitration catalyzed by glyoxalase domain containing protein 4.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Research progress on the α-synuclein-lysosome axis in Parkinson's disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting.Frontiers in neuroscience · 2026Review
- Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.Frontiers in pharmacology · 2026Review
- Metabolic reprogramming and altered ATP content impair neuroprotective functions of microglia in β-glucocerebrosidase deficiency models.Journal of neuroinflammation · 2025Article
- Review
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Lactoferrin as a Candidate Multifunctional Therapeutic in Synucleinopathies.Brain sciences · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
In this study, heterozygous expression of a common Parkinson-associated GBA1 variant, the L444P mutation, was found to exacerbate α-synuclein aggregation and spreading in a mouse model of Parkinson-like pathology targeting neurons of the medullary vagal system. These neurons were also shown to become more vulnerable to oxidative and nitrative stress after L444P expression. The latter paralleled neuronal formation of reactive oxygen species and led to a pronounced accumulation of nitrated α-synuclein. A causal relationship linked mutation-induced oxidative/nitrative stress to enhanced α-synuclein aggregation and spreading that could indeed be rescued by neuronal overexpression of mitochondrial superoxide dismutase 2. Further evidence supported a key involvement of mitochondria as sources of reactive oxygen species as well as targets of oxidative and nitrative damage within L444P-expressing neurons. These findings support the conclusion that enhanced vulnerability to mitochondrial oxidative stress should be considered an important mechanism predisposing to pathology conversion in carriers of GBA1 mutations.
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Registered trials
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