ArticleHuman molecular genetics2008
Compensatory changes in the ubiquitin-proteasome system, brain-derived neurotrophic factor and mitochondrial complex II/III in YAC72 and R6/2 transgenic mice partially model Huntington's disease patients.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Inhibition of UBE2N promotes the clearance of mutant HTT (huntingtin) in HD knock-in mice.Autophagy · 2025Article
- Brain-Derived Neurotrophic Factor (BDNF) in Huntington's Disease: Neurobiology and Therapeutic Potential.Current neuropharmacology · 2025Review
- Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier.MedComm · 2024Review
- Large animal models for Huntington's disease research.Zoological research · 2024Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Matrix Metalloproteinase-8 Inhibitor Ameliorates Inflammatory Responses and Behavioral Deficits in LRRK2 G2019S Parkinson's Disease Model Mice.Biomolecules & therapeutics · 2021Article
- The Effects of Selective Inhibition of Histone Deacetylase 1 and 3 in Huntington's Disease Mice.Frontiers in molecular neuroscience · 2021Article
- HDAC Inhibition by Valproic Acid Induces Neuroprotection and Improvement of PD-like Behaviors in LRRK2 R1441G Transgenic Mice.Experimental neurobiology · 2019Article
- FOXOs modulate proteasome activity in human-induced pluripotent stem cells of Huntington's disease and their derived neural cells.Human molecular genetics · 2017Article
- Laquinimod treatment in the R6/2 mouse model.Scientific reports · 2017Article
- Cognitive dysfunction in Huntington's disease: mechanisms and therapeutic strategies beyond BDNF.Brain pathology (Zurich, Switzerland) · 2016Review
- A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease.Human molecular genetics · 2016Article
- Impaired TrkB Signaling Underlies Reduced BDNF-Mediated Trophic Support of Striatal Neurons in the R6/2 Mouse Model of Huntington's Disease.Frontiers in cellular neuroscience · 2016Article
- Selective reduction of striatal mature BDNF without induction of proBDNF in the zQ175 mouse model of Huntington's disease.Neurobiology of disease · 2015Article
- A mitochondrial basis for Huntington's disease: therapeutic prospects.Molecular and cellular biochemistry · 2014Review
- A role of mitochondrial complex II defects in genetic models of Huntington's disease expressing N-terminal fragments of mutant huntingtin.Human molecular genetics · 2013Article
- Review
- Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease.PloS one · 2011Article
- BDNF overexpression in the forebrain rescues Huntington's disease phenotypes in YAC128 mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Methylenedioxymethamphetamine inhibits mitochondrial complex I activity in mice: a possible mechanism underlying neurotoxicity.British journal of pharmacology · 2010Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Intraneuronal protein aggregates of the mutated huntingtin in Huntington's disease (HD) brains suggest an overload and/or dysfunction of the ubiquitin-proteasome system (UPS). There is a general inhibition of the UPS in many brain regions (cerebellum, cortex, substantia nigra and caudate-putamen) and skin fibroblasts from HD patients. In the current experiment, the widely used mutant huntingtin-exon 1 CAG repeat HD transgenic mice model (R6/2) (with 144 CAG repeat and exon 1) during late-stage pathology, had increases in proteasome activity in the striatum. However, this discrepancy with HD patient tissue was not apparent in the mutant CAG repeat huntingtin full-length HD (YAC72) transgenic mouse model during post-symptomatic and late-stage pathology, which then also showed UPS inhibition similar to HD patients' brains. In both types of HD model mice, we determined biochemical changes, including expression of brain-derived neurotrophic factor (BDNF) and mitochondrial complex II/III (MCII/III) activities related to HD pathology. We found increases of both BDNF expression, and MCII/III activities in YAC72 transgenic mice, and no change of BDNF expression in R6/2 mice. Our data show that extreme CAG repeat lengths in R6/2 mice is paradoxically associated with increased proteasome activity, probably as a cellular compensatory biochemical change in response to the underlying mutation. Changes in HD patients for UPS function, BDNF expression and MCII/III activity are only partially modeled in R6/2 and YAC72 mice, with the latter at 16 months of age being most congruent with the human disease.
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