ArticleThe Journal of biological chemistry2022
Glycation modulates alpha-synuclein fibrillization kinetics: A sweet spot for inhibition.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- From Glycation to Toxicity: α-Synuclein Oligomers, Oxidative Stress, and Multi-Targeted Protection by Trans-Ferulic Acid.Cell biochemistry and biophysics · 2026Article
- Effects of Site-Specific Glycation on α-Synuclein.ACS chemical biology · 2026Article
- Protein glycoxidation in neuropsychiatric disorders-from basic research to clinical practice.Redox biology · 2026Review
- Determination of α-Synuclein Protein Interactions by μMap Photoproximity Labeling.Journal of the American Chemical Society · 2026Article
- Protein misfolding: understanding biology to classify and treat synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses.NPJ Parkinson's disease · 2025Article
- Determination of α-Synuclein Protein Interactions by μMap Photo-proximity Labeling.bioRxiv : the preprint server for biology · 2025Article
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- Interaction Between α-Synuclein and DJ-1 in Parkinson's Disease.Brain sciences · 2025Review
- Glycation of Proteins and Its End Products: From Initiation to Natural Product-Based Therapeutic Preventions.ACS pharmacology & translational science · 2025Review
- Non-enzymatic posttranslational protein modifications in protein aggregation and neurodegenerative diseases.RSC chemical biology · 2025Review
- In Vivo UV-Induced Fluorescence Spectroscopy of Skin in Parkinson's Disease.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2025Article
- Subtle concentration changes in zinc hold the key to fibrillation of α-synuclein: an updated insight on the micronutrient's role in prevention of neurodegenerative disorders.Frontiers in molecular biosciences · 2025Review
- Methylglyoxal-Induced Modifications in Human Triosephosphate Isomerase: Structural and Functional Repercussions of Specific Mutations.Molecules (Basel, Switzerland) · 2024Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.International journal of molecular sciences · 2024Review
- D-ribose metabolic disorder and diabetes mellitus.Molecular biology reports · 2024Review
- Diabetes and Parkinson's Disease: Understanding Shared Molecular Mechanisms.Journal of Parkinson's disease · 2024Review
- RAGE Against the Glycation Machine in Synucleinopathies: Time to Explore New Questions.Journal of Parkinson's disease · 2023Review
- Ribose Intake as Food Integrator: Is It a Really Convenient Practice?Biomolecules · 2022Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycation is a nonenzymatic posttranslational modification (PTM) known to be increased in the brains of hyperglycemic patients. Alpha-synuclein (αSN), a central player in the etiology of Parkinson's disease, can be glycated at lysine residues, thereby reducing αSN fibril formation in vitro and modulating αSN aggregation in cells. However, the molecular basis for these effects is unclear. To elucidate this, we investigated the aggregation of αSN modified by eight glycating agents, namely the dicarbonyl compound methylglyoxal (MGO) and the sugars ribose, fructose, mannose, glucose, galactose, sucrose, and lactose. We found that MGO and ribose modify αSN to the greatest extent, and these glycation products are the most efficient inhibitors of fibril formation. We show glycation primarily inhibits elongation rather than nucleation of αSN and has only a modest effect on the level of oligomerization. Furthermore, glycated αSN is not significantly incorporated into fibrils. For both MGO and ribose, we discovered that a level of ∼5 modifications per αSN is optimal for inhibition of elongation. The remaining sugars showed a weak but optimal inhibition at ∼2 modifications per αSN. We propose that this optimal level balances the affinity for the growing ends of the fibril (which decreases with the extent of modification) with the ability to block incorporation of subsequent αSN subunits (which increases with modification). Our results are not only relevant for other αSN PTMs but also for understanding PTMs affecting other fibrillogenic proteins and may thus open novel avenues for therapeutic intervention in protein aggregation disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.