ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Quantitative relationships between huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into huntington's disease molecular pathogenesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 165 citations in OpenAlex.
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- TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.Cell reports · 2025Article
- Differential response of neurons to autophagy modulation in Huntington's disease.Autophagy reports · 2025Article
- Peripheral sequestration of huntingtin delays neuronal death and depends on N-terminal ubiquitination.Communications biology · 2024Article
- TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.bioRxiv : the preprint server for biology · 2024Article
- 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
- Review
- Biological Potential, Gastrointestinal Digestion, Absorption, and Bioavailability of Algae-Derived Compounds with Neuroprotective Activity: A Comprehensive Review.Marine drugs · 2022Review
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
- Superhuman cell death detection with biomarker-optimized neural networks.Science advances · 2021Article
- Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties.Nature communications · 2021Article
- Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration.Nature communications · 2021Article
- "Protein aggregates" contain RNA and DNA, entrapped by misfolded proteins but largely rescued by slowing translational elongation.Aging cell · 2021Article
- Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells.PloS one · 2021Article
- Nicotinamide Adenine Dinucleotide Phosphate Oxidases Are Everywhere in Brain Disease, but Not in Huntington's Disease?Frontiers in aging neuroscience · 2021Review
- Functional genomics, genetic risk profiling and cell phenotypes in neurodegenerative disease.Neurobiology of disease · 2020Review
- Ubiquilin-2 differentially regulates polyglutamine disease proteins.Human molecular genetics · 2020Article
- Site-specific ubiquitination of pathogenic huntingtin attenuates its deleterious effects.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review
- Expression of mutant exon 1 huntingtin fragments in human neural stem cells and neurons causes inclusion formation and mitochondrial dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
An expanded polyglutamine (polyQ) stretch in the protein huntingtin (htt) induces self-aggregation into inclusion bodies (IBs) and causes Huntington's disease (HD). Defining precise relationships between early observable variables and neuronal death at the molecular and cellular levels should improve our understanding of HD pathogenesis. Here, we used an automated microscope that tracks thousands of neurons individually over their entire lifetime to quantify interconnected relationships between early variables, such as htt levels, polyQ length, and IB formation, and neuronal death in a primary striatal model of HD. The resulting model revealed that mutant htt increases the risk of death by tonically interfering with homeostatic coping mechanisms rather than producing accumulated damage to the neuron, htt toxicity is saturable, the rate-limiting steps for inclusion body formation and death can be traced to different conformational changes in monomeric htt, and IB formation reduces the impact of the starting levels of htt of a neuron on its risk of death. Finally, the model that emerges from our quantitative measurements places critical limits on the potential mechanisms by which mutant htt might induce neurodegeneration, which should help direct future research.
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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.