ArticleThe Journal of cell biology2013
Synaptic mutant huntingtin inhibits synapsin-1 phosphorylation and causes neurological symptoms.
Article in The Journal of cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- Restoration of Sleep and Circadian Behavior by Autophagy Modulation in Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Rapamycin reduces neuronal mutant huntingtin aggregation and ameliorates locomotor performance inFrontiers in aging neuroscience · 2023Article
- Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression.Drug design, development and therapy · 2022Article
- Disposition of Proteins and Lipids in Synaptic Membrane Compartments Is Altered in Q175/Q7 Huntington's Disease Mouse Striatum.Frontiers in synaptic neuroscience · 2021Article
- SIV-Mediated Synaptic Dysfunction Is Associated with an Increase in Synapsin Site 1 Phosphorylation and Impaired PP2A Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update. II. Hyperkinetic disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2019Review
- The Role of Synapsins in Neurological Disorders.Neuroscience bulletin · 2018Review
- Molecular insights into cortico-striatal miscommunications in Huntington's disease.Current opinion in neurobiology · 2018Review
- Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls.Aging cell · 2016Article
- Compartment-Dependent Degradation of Mutant Huntingtin Accounts for Its Preferential Accumulation in Neuronal Processes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- Aged monkey brains reveal the role of ubiquitin-conjugating enzyme UBE2N in the synaptosomal accumulation of mutant huntingtin.Human molecular genetics · 2015Article
- Large Animal Models of Huntington's Disease.Current topics in behavioral neurosciences · 2015Review
- Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy.Drug design, development and therapy · 2015Review
- Ubiquitin-activating enzyme activity contributes to differential accumulation of mutant huntingtin in brain and peripheral tissues.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Striatal synaptosomes from Hdh140Q/140Q knock-in mice have altered protein levels, novel sites of methionine oxidation, and excess glutamate release after stimulation.Journal of Huntington's disease · 2013Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Many genetic mouse models of Huntington's disease (HD) have established that mutant huntingtin (htt) accumulates in various subcellular regions to affect a variety of cellular functions, but whether and how synaptic mutant htt directly mediates HD neuropathology remains to be determined. We generated transgenic mice that selectively express mutant htt in the presynaptic terminals. Although it was not overexpressed, synaptic mutant htt caused age-dependent neurological symptoms and early death in mice as well as defects in synaptic neurotransmitter release. Mass spectrometry analysis of synaptic fractions and immunoprecipitation of synapsin-1 from HD CAG150 knockin mouse brains revealed that mutant htt binds to synapsin-1, a protein whose phosphorylation is critical for neurotransmitter release. We found that polyglutamine-expanded exon1 htt binds to the C-terminal region of synapsin-1 to reduce synapsin-1 phosphorylation. Our findings point to a critical role for synaptic htt in the neurological symptoms of HD, providing a new therapeutic target.
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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.