ArticleScience advances2021
Increasing brain palmitoylation rescues behavior and neuropathology in Huntington disease mice.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- A dual-targeting mRNA lipid nanoparticle restores ABCA1-dependent cholesterol homeostasis to promote repair of age-related bone defects.Bioactive materials · 2027Article
- Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment.iScience · 2026Article
- ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- A novel approach to combatMicrobiology spectrum · 2026Article
- The Roles of ProteinCancer communications (London, England) · 2026Review
- Palmitoylation reprograms the intestinal mucosal barrier microenvironment: potential mechanisms and promising therapeutic targets.Frontiers in pharmacology · 2026Review
- SQSTM1/p62 UFMylation Enhances Autophagic Clearance of Pathogenic Mutant Huntingtin.International journal of biological sciences · 2026Article
- A Novel Palmitoylation-Related Molecular Signature for Predicting and Therapeutically Targeting Alzheimer's Disease.Molecular neurobiology · 2025Article
- Post-Translational Modifications of Huntingtin: Mechanistic Insights and Therapeutic Opportunities in Huntington's Disease.International journal of molecular sciences · 2025Review
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- Fat traffic control: S-acylation in axonal transport.Molecular pharmacology · 2025Review
- Reduced Palmitoylation of SQSTM1/p62 in Huntington Disease Is Associated With Impaired Autophagy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- S-acylation in apoptotic and non-apoptotic cell death: a central regulator of membrane dynamics and protein function.Biochemical Society transactions · 2025Review
- Engineered depalmitoylases enable selective manipulation of protein localization and function.Nature communications · 2025Article
- Review
- Article
- Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- A palmitoyl transferase chemical-genetic system to map ZDHHC-specific S-acylation.Nature biotechnology · 2024Article
- Regulation of autophagy by protein lipidation.Advanced biotechnology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington disease (HD) damages the corticostriatal circuitry in large part by impairing transport of brain-derived neurotrophic factor (BDNF). We hypothesized that improving vesicular transport of BDNF could slow or prevent disease progression. We therefore performed selective proteomic analysis of vesicles transported within corticostriatal projecting neurons followed by in silico screening and identified palmitoylation as a pathway that could restore defective huntingtin-dependent trafficking. Using a synchronized trafficking assay and an HD network-on-a-chip, we found that increasing brain palmitoylation via ML348, which inhibits the palmitate-removing enzyme acyl-protein thioesterase 1 (APT1), restores axonal transport, synapse homeostasis, and survival signaling to wild-type levels without toxicity. In human HD induced pluripotent stem cell-derived cortical neurons, ML348 increased BDNF trafficking. In HD knock-in mice, it efficiently crossed the blood-brain barrier to restore palmitoylation levels and reverse neuropathology, locomotor deficits, and anxio-depressive behaviors. APT1 and its inhibitor ML348 thus hold therapeutic interest for HD.
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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.