ArticleCellular and molecular life sciences : CMLS2023
Soluble mutant huntingtin drives early human pathogenesis in Huntington's disease.
Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- miR-196a reduces mutant Huntingtin aggregates by Rad23b-mediated degradation in Huntington's disease.Journal of biomedical science · 2026Article
- Memory Impairments: Type, Causes, and Molecular Players-Memory Dysfunction Across Neurologic Insults.Cells · 2026Review
- The Evolving Landscape of Stem Cell Therapies for Huntington's Disease.Molecular diagnosis & therapy · 2026Review
- Extracellular vesicle-based therapies for neurodegenerative diseases.NeuroImmune pharmacology and therapeutics · 2025Review
- Small Extracellular Vesicles in Neurodegenerative Disease: Emerging Roles in Pathogenesis, Biomarker Discovery, and Therapy.International journal of molecular sciences · 2025Review
- Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons.Stem cells (Dayton, Ohio) · 2025Article
- Mitochondria from huntington´s disease striatal astrocytes are hypermetabolic and compromise neuronal branching.Cell communication and signaling : CCS · 2025Article
- An Updated and Comprehensive Review Exploring the Gut-Brain Axis in Neurodegenerative Disorders and Neurotraumas: Implications for Therapeutic Strategies.Brain sciences · 2025Review
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular mechanisms of amyloid inhibition: an NMR-driven framework with polyphenols as a case study.Frontiers in molecular biosciences · 2025Article
- Brain-derived extracellular vesicles potentially mediate crosstalk with peripheral organs in neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Therapeutic approaches targeting aging and cellular senescence in Huntington's disease.CNS neuroscience & therapeutics · 2024Review
- Motor skill learning modulates striatal extracellular vesicles' content in a mouse model of Huntington's disease.Cell communication and signaling : CCS · 2024Article
- Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in-tissue multiscale 3D electron microscopy.Acta neuropathologica communications · 2024Article
- Exosomes for neurodegenerative diseases: diagnosis and targeted therapy.Journal of neurology · 2024Review
- Role of TFEB in Huntington's Disease.Biology · 2024Review
- Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Unlocking the potential of circulating small extracellular vesicles in neurodegenerative disease through targeted biomarkers and advancements in biosensing.Exploration of biomat-x · 2024Article
- Transmission-selective muscle pathology induced by the active propagation of mutant huntingtin across the human neuromuscular synapse.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
Abstract
Huntington's disease (HD) is an incurable inherited brain disorder characterised by massive degeneration of striatal neurons, which correlates with abnormal accumulation of misfolded mutant huntingtin (mHTT) protein. Research on HD has been hampered by the inability to study early dysfunction and progressive degeneration of human striatal neurons in vivo. To investigate human pathogenesis in a physiologically relevant context, we transplanted human pluripotent stem cell-derived neural progenitor cells (hNPCs) from control and HD patients into the striatum of new-born mice. Most hNPCs differentiated into striatal neurons that projected to their target areas and established synaptic connexions within the host basal ganglia circuitry. Remarkably, HD human striatal neurons first developed soluble forms of mHTT, which primarily targeted endoplasmic reticulum, mitochondria and nuclear membrane to cause structural alterations. Furthermore, HD human cells secreted extracellular vesicles containing mHTT monomers and oligomers, which were internalised by non-mutated mouse striatal neurons triggering cell death. We conclude that interaction of mHTT soluble forms with key cellular organelles initially drives disease progression in HD patients and their transmission through exosomes contributes to spread the disease in a non-cell autonomous manner.
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What OpenQuestion holds
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.