ArticleNeuromolecular medicine2014
Early down-regulation of PKCδ as a pro-survival mechanism in Huntington's disease.
Article in Neuromolecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Article
- PKCδ Regulates DNA Damage and Cell Death through a SIRT6/Nrf2-dependent Antioxidant Response.Molecular cancer research : MCR · 2025Article
- Down-regulation of neuroprotective protein kinase D in Huntington´s disease.Cell death & disease · 2025Article
- Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.bioRxiv : the preprint server for biology · 2025Article
- A Nuclear Belt Fastens on Neural Cell Fate.Cells · 2022Review
- Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease.EMBO molecular medicine · 2021Article
- Age-related and disease locus-specific mechanisms contribute to early remodelling of chromatin structure in Huntington's disease mice.Nature communications · 2021Article
- Increased Levels of Rictor Prevent Mutant Huntingtin-Induced Neuronal Degeneration.Molecular neurobiology · 2018Article
- Herp Promotes Degradation of Mutant Huntingtin: Involvement of the Proteasome and Molecular Chaperones.Molecular neurobiology · 2018Article
- Cognitive dysfunction in Huntington's disease: mechanisms and therapeutic strategies beyond BDNF.Brain pathology (Zurich, Switzerland) · 2016Review
- RTP801 Is Involved in Mutant Huntingtin-Induced Cell Death.Molecular neurobiology · 2016Article
- Compensatory mechanisms in genetic models of neurodegeneration: are the mice better than humans?Frontiers in cellular neuroscience · 2015Review
- The unfolded protein response and its potential role in Huntington's disease elucidated by a systems biology approach.F1000Research · 2015Article
- Possible involvement of self-defense mechanisms in the preferential vulnerability of the striatum in Huntington's disease.Frontiers in cellular neuroscience · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A balance between cell survival and apoptosis is crucial to avoid neurodegeneration. Here, we analyzed whether the pro-apoptotic protein PKCδ, and the pro-survival PKCα and βII, were dysregulated in the brain of R6/1 mouse model of Huntington's disease (HD). Protein levels of the three PKCs examined were reduced in all the brain regions analyzed being PKCδ the most affected isoform. Interestingly, PKCδ protein levels were also decreased in the striatum and cortex of R6/2 and Hdh(Q111/Q111) mice, and in the putamen of HD patients. Nuclear PKCδ induces apoptosis, but we detected reduced PKCδ in both cytoplasmic and nuclear enriched fractions from R6/1 mouse striatum, cortex and hippocampus. In addition, we show that phosphorylation and ubiquitination of PKCδ are increased in 30-week-old R6/1 mouse brain. All together these results suggest a pro-survival role of reduced PKCδ levels in response to mutant huntingtin-induced toxicity. In fact, we show that over-expression of PKCδ increases mutant huntingtin-induced cell death in vitro, whereas over-expression of a PKCδ dominant negative form or silencing of endogenous PKCδ partially blocks mutant huntingtin-induced cell death. Finally, we show that the analysis of lamin B protein levels could be a good marker of PKCδ activity, but it is not involved in PKCδ-mediated cell death in mutant huntingtin-expressing cells. In conclusion, our results suggest that neurons increase the degradation of PKCδ as a compensatory pro-survival mechanism in response to mutant huntingtin-induced toxicity that can help to understand why cell death appears late in the disease.
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