ArticleNeuron2015
Reinstating aberrant mTORC1 activity in Huntington's disease mice improves disease phenotypes.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 166 citations in OpenAlex.
- Article
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Metabolic reprogramming in neurodegenerative diseases: New insights into mTOR-mediated microglial polarization.Journal of translational internal medicine · 2025Article
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- Article
- Antioxidant and Anti-Inflammatory Defenses in Huntington's Disease: Roles of NRF2 and PGC-1α, and Therapeutic Strategies.Life (Basel, Switzerland) · 2025Review
- Mechanistic insights on the role of Nrf-2 signalling in Huntington's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- CCT and Cullin1 Regulate the TORC1 Pathway to Promote Dendritic Arborization in Health and Disease.Cells · 2024Article
- Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Branched-chain amino acids and the risks of dementia, Alzheimer's disease, and Parkinson's disease.Frontiers in aging neuroscience · 2024Article
- Investigating Neuron Degeneration in Huntington's Disease Using RNA-Seq Based Transcriptome Study.Genes · 2023Article
- Cholecystokinin Activation of Cholecystokinin 1 Receptors: a Purkinje Cell Neuroprotective Pathway.Cerebellum (London, England) · 2023Review
- VGLUT3 Deletion Rescues Motor Deficits and Neuronal Loss in the zQ175 Mouse Model of Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Rasd2 Mediates Acute Fasting-Induced Antidepressant-Like Effects via Dopamine D2 Receptor Activation in Ovariectomized Mice.The international journal of neuropsychopharmacology · 2023Article
- Rhes depletion promotes striatal accumulation and aggregation of mutant huntingtin in a presymptomatic HD mouse model.Frontiers in aging neuroscience · 2023Article
- The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.Current neurovascular research · 2023Article
- Distinct subcellular autophagy impairments in induced neurons from patients with Huntington's disease.Brain : a journal of neurology · 2022Article
- The Interaction ofCells · 2022Review
- Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy.Translational psychiatry · 2022Review
- Huntington's disease phenotypes are improved via mTORC1 modulation by small molecule therapy.PloS one · 2022Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Huntington's disease (HD) is caused by a polyglutamine tract expansion in huntingtin (HTT). Despite HTTs ubiquitous expression, there is early and robust vulnerability in striatum, the cause of which is poorly understood. Here, we provide evidence that impaired striatal mTORC1 activity underlies varied metabolic and degenerative phenotypes in HD brain and show that introducing the constitutively active form of the mTORC1 regulator, Rheb, into HD mouse brain, alleviates mitochondrial dysfunction, aberrant cholesterol homeostasis, striatal atrophy, impaired dopamine signaling, and increases autophagy. We also find that the expression of Rhes, a striatum-enriched mTOR activator, is reduced in HD patient and mouse brain and that exogenous addition of Rhes alleviates motor deficits and improves brain pathology in HD mice. Our combined work indicates that impaired Rhes/mTORC1 activity in HD brain may underlie the notable striatal susceptibility and thus presents a promising therapeutic target for HD therapy.
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