ArticleAging cell2023
N-homocysteinylation of α-synuclein promotes its aggregation and neurotoxicity.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Association between the risk and severity of Parkinson's disease and plasma homocysteine, vitamin B12 and folate levels: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2023Pooled it
- N-Homocysteinylation of Cofilin-1 Aggravates Epileptic Pathophysiology via Disruption of Actin Dynamics.Neuroscience bulletin · 2026Article
- Neuroprotective effects of lixisenatide against propagation of α-synuclein pathology in Parkinson's disease.Neural regeneration research · 2026Article
- Homocysteine increases phosphorylation and aggregation of α-synuclein.Journal of clinical biochemistry and nutrition · 2026Article
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- Serum Homocysteine as a Potential Dynamic Biomarker for Staging and Monitoring Progression in Alzheimer's Disease.Neuropsychiatric disease and treatment · 2026Article
- Homocysteine interferes with Ndufa1 leading to mitochondrial dysfunction through repression of the NADCell death & disease · 2025Article
- N-Homocysteinylation of lysine residues in α-Synuclein enhances aggregation propensity and cytotoxicity in SH-SY5Y cells.Scientific reports · 2025Article
- Lower water-soluble vitamins and higher homocysteine are associated with neurodegenerative diseases.Scientific reports · 2025Article
- N-Homocysteinylation of HMGB1/2 Promotes Corpus Cavernosum Endothelial Senescence in Erectile Dysfunction.International journal of biological sciences · 2025Article
- Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Parkinson's disease and vitamins: a focus on vitamin B12.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- The Imbalance of Homocysteine, Vitamin B12 and Folic Acid in Parkinson Plus Syndromes: A Review beyond Parkinson Disease.Biomolecules · 2024Review
- Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Article
- Association of plasma homocysteine with cognitive impairment in patients with Parkinson's disease.Frontiers in aging neuroscience · 2024Article
- Inhibition of abnormal C/EBPβ/α-Syn signaling pathway through activation of Nrf2 ameliorates Parkinson's disease-like pathology.Aging cell · 2023Article
- Article
- Deletion of the Homocysteine Thiolactone Detoxifying Enzyme Bleomycin Hydrolase, in Mice, Causes Memory and Neurological Deficits and Worsens Alzheimer's Disease-Related Behavioral and Biochemical Traits in the 5xFAD Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggregation of α-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease (PD). Epidemiological evidence indicates that high level of homocysteine (Hcy) is associated with an increased risk of PD. However, the molecular mechanisms remain elusive. Here, we report that homocysteine thiolactone (HTL), a reactive thioester of Hcy, covalently modifies α-synuclein on the K80 residue. The levels of α-synuclein K80Hcy in the brain are increased in an age-dependent manner in the TgA53T mice, correlating with elevated levels of Hcy and HTL in the brain during aging. The N-homocysteinylation of α-synuclein stimulates its aggregation and forms fibrils with enhanced seeding activity and neurotoxicity. Intrastriatal injection of homocysteinylated α-synuclein fibrils induces more severe α-synuclein pathology and motor deficits when compared with unmodified α-synuclein fibrils. Increasing the levels of Hcy aggravates α-synuclein neuropathology in a mouse model of PD. In contrast, blocking the N-homocysteinylation of α-synuclein ameliorates α-synuclein pathology and degeneration of dopaminergic neurons. These findings suggest that the covalent modification of α-synuclein by HTL promotes its aggregation. Targeting the N-homocysteinylation of α-synuclein could be a novel therapeutic strategy against PD.
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