ArticleScientific reports2021
Acetylation turns leucine into a drug by membrane transporter switching.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Neurofilament light chain (NfL) as a surrogate outcome measure for GM2 gangliosidoses.Journal of neurology · 2026Trial
- Disease-Modifying, Neuroprotective Effect of N-Acetyl-l-Leucine in Adult and Pediatric Patients With Niemann-Pick Disease Type C.Neurology · 2025Trial
- Trial
- Efficacy and Safety of N-Acetyl-l-Leucine in Children and Adults With GM2 Gangliosidoses.Neurology · 2023Trial
- Recent Advances in Therapy for the Neurodegenerative Disorder Ataxia-Telangiectasia.International journal of molecular sciences · 2026Review
- Synthesis of N-Acetyl-D- and -L-Leucine-ChemMedChem · 2026Article
- N-acetyl-L-leucine in Neurological Disorders: Mechanisms, Evidence, and Therapeutic Perspectives.Cerebellum (London, England) · 2026Review
- Relationships between immune cells, blood metabolites, and intrahepatic cholangiocarcinoma: a Mendelian randomization study with experimental validation.Frontiers in cell and developmental biology · 2026Article
- Article
- Neuromodulatory effects of N-acetyl-L-leucine in a human induced neuronal cell culture system.Frontiers in immunology · 2026Article
- Limited therapeutic efficacy of N-acetyl-L-leucine in a mouse model of CLN1 disease.Scientific reports · 2025Article
- Symptomatic Benefit of Acetyl-DL-Leucine for Cerebellar Ataxia in Juvenile Tay-Sachs Disease: A Pediatric Case and Literature Review.Molecular syndromology · 2025Article
- Acetyl-DL-leucine (Tanganil™) in three patients with advanced multiple system atrophy.BMC neurology · 2025Article
- "How to save a marriage": treatment of REM sleep behavior disorder (RBD) with acetyl-leucine in a patient with Parkinson's disease.Journal of neurology · 2025Article
- Acetyl-DL-leucine in two individuals with REM sleep behavior disorder improves symptoms, reverses loss of striatal dopamine-transporter binding and stabilizes pathological metabolic brain pattern-case reports.Nature communications · 2024Article
- The Impact of Glycolysis and Its Inhibitors on the Immune Response to Inflammation and Autoimmunity.Molecules (Basel, Switzerland) · 2024Review
- Review
- Acetyl-DL-leucine in combination with memantine improves acquired pendular nystagmus caused by multiple sclerosis: a case report.Journal of neurology · 2023Article
- Article
- FDA approval of Miplyffa and Aqneursa: A dual breakthrough for the treatment of Neimann-Pick disease type C.Alzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Small changes to molecules can have profound effects on their pharmacological activity as exemplified by the addition of the two-carbon acetyl group to make drugs more effective by enhancing their pharmacokinetic or pharmacodynamic properties. N-acetyl-D,L-leucine is approved in France for vertigo and its L-enantiomer is being developed as a drug for rare and common neurological disorders. However, the precise mechanistic details of how acetylation converts leucine into a drug are unknown. Here we show that acetylation of leucine switches its uptake into cells from the L-type amino acid transporter (LAT1) used by leucine to organic anion transporters (OAT1 and OAT3) and the monocarboxylate transporter type 1 (MCT1). Both the kinetics of MCT1 (lower affinity compared to LAT1) and the ubiquitous tissue expression of MCT1 make it well suited for uptake and distribution of N-acetyl-L-leucine. MCT1-mediated uptake of a N-acetyl-L-leucine as a prodrug of leucine bypasses LAT1, the rate-limiting step in activation of leucine-mediated signalling and metabolic process inside cells such as mTOR. Converting an amino acid into an anion through acetylation reveals a way for the rational design of drugs to target anion transporters.
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Registered trials
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.