ArticleNature communications2024
Mutant huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Cortical organoids reveal human-specific role of METTL5 in neurodevelopment via regulation of CHCHD2.Stem cell reports · 2026Article
- Review
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- Insights into neurodevelopmental features of Huntington's disease from stem cell-derived models including organoids.Journal of Huntington's disease · 2026Review
- Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy.Cell · 2026Article
- Article
- Exploring huntington's disease from a neurodevelopmental perspective.International journal of biological sciences · 2026Review
- Are neurodegenerative diseases late-onset neurodevelopmental disorders? Tracing the developmental origins of neuronal vulnerability.Frontiers in neuroscience · 2026Review
- A review of neuroprotective properties ofAnnals of medicine · 2025Review
- CLN7 protein functions at the interface between endolysosomes and stress granules to promote cell survival.Cell death & disease · 2025Article
- Neuronal branching in stem cell models of mitochondrial and neurological diseases.Stem cells (Dayton, Ohio) · 2025Review
- The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain.Cell death & disease · 2025Article
- Brain organoid models of Huntington's disease shift the focus towards neurodevelopment.Disease models & mechanisms · 2025Article
- Review
- METAB-HTX: prospective, longitudinal cohort study evaluating cardiac and systemic metabolism after heart transplantation.ESC heart failure · 2025Article
- Role of the mitochondrial regulatory factor CHCHD2 in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Morphogenetic Designs, and Disease Models in Central Nervous System Organoids.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
39 authors.
Funding
Abstract
Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington's disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.
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