ArticleNature communications2023
Chemoproteomic target deconvolution reveals Histone Deacetylases as targets of (R)-lipoic acid.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Small-molecule dissolution of stress granules by redox modulation benefits ALS models.Nature chemical biology · 2025Article
- Current perspectives in drug targeting intrinsically disordered proteins and biomolecular condensates.BMC biology · 2025Review
- α-Lipoic acid mitigates age-related macular degeneration via ferroptosis: integrative multi-omics and network pharmacology.Frontiers in pharmacology · 2025Article
- An advanced chitosan based sponges dressing system with antioxidative, immunoregulation, angiogenesis and neurogenesis for promoting diabetic wound healing.Materials today. Bio · 2024Article
- HDAC1 Promotes Mitochondrial Pathway Apoptosis and Inhibits the Endoplasmic Reticulum Stress Response in High Glucose-Treated Schwann Cells via Decreased U4 Spliceosomal RNA.Neurochemical research · 2024Article
- The Antioxidant and HDAC-Inhibitor α-Lipoic Acid Is Synergistic with Exemestane in Estrogen Receptor-Positive Breast Cancer Cells.International journal of molecular sciences · 2024Article
- OmicScope unravels systems-level insights from quantitative proteomics data.Nature communications · 2024Article
- Nanotechnological Approaches to Enhance the Potential of α-Lipoic Acid for Application in the Clinic.Antioxidants (Basel, Switzerland) · 2024Review
- A laser flash photolysis study of the free radical chemistry of lipoic acid and dihydrolipoic acid.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2023Article
- Crystal structure of histone deacetylase 6 complexed with (R)-lipoic acid, an essential cofactor in central carbon metabolism.The Journal of biological chemistry · 2023Article
- Crystal Structure of Histone Deacetylase 6 Complexed with (bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipoic acid is an essential enzyme cofactor in central metabolic pathways. Due to its claimed antioxidant properties, racemic (R/S)-lipoic acid is used as a food supplement but is also investigated as a pharmaceutical in over 180 clinical trials covering a broad range of diseases. Moreover, (R/S)-lipoic acid is an approved drug for the treatment of diabetic neuropathy. However, its mechanism of action remains elusive. Here, we performed chemoproteomics-aided target deconvolution of lipoic acid and its active close analog lipoamide. We find that histone deacetylases HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are molecular targets of the reduced form of lipoic acid and lipoamide. Importantly, only the naturally occurring (R)-enantiomer inhibits HDACs at physiologically relevant concentrations and leads to hyperacetylation of HDAC substrates. The inhibition of HDACs by (R)-lipoic acid and lipoamide explain why both compounds prevent stress granule formation in cells and may also provide a molecular rationale for many other phenotypic effects elicited by lipoic acid.
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Registered trials
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