ArticleNeurobiology of disease2011
Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6.
Article in Neurobiology of disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Commentary to: "The Pathophysiology and Clinical Manifestations of Spinocerebellar Ataxia Type 6" by Rentiya et al., Cerebellum 2020;19(3):459-464).Cerebellum (London, England) · 2021Article
- Recent advances in molecular therapies for neurological disease: triplet repeat disorders.Human molecular genetics · 2019Review
- CAV2 promotes the growth of renal cell carcinoma through the EGFR/PI3K/Akt pathway.OncoTargets and therapy · 2018Article
- Interaction of the polyglutamine protein ataxin-3 with Rad23 regulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3.Human molecular genetics · 2017Article
- Spinocerebellar ataxia type 6 protein aggregates cause deficits in motor learning and cerebellar plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.Nature genetics · 2015Article
- Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23.Nature communications · 2014Article
- Consensus paper: management of degenerative cerebellar disorders.Cerebellum (London, England) · 2014Article
- Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias.Cerebellum (London, England) · 2014Article
- Silencing mutant ATXN3 expression resolves molecular phenotypes in SCA3 transgenic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Article
- Recent advances in RNA interference therapeutics for CNS diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2013Review
- Altered Purkinje cell miRNA expression and SCA1 pathogenesis.Neurobiology of disease · 2013Article
- Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics.Orphanet journal of rare diseases · 2013Review
- Recent advances in the genetics of cerebellar ataxias.Current neurology and neuroscience reports · 2012Review
- Cell biology of spinocerebellar ataxia.The Journal of cell biology · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Spinocerebellar ataxia type 6 (SCA6) is an inherited neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the Ca(V)2.1 voltage-gated calcium channel subunit (CACNA1A). There is currently no treatment for this debilitating disorder and thus a pressing need to develop preventative therapies. RNA interference (RNAi) has proven effective at halting disease progression in several models of spinocerebellar ataxia (SCA), including SCA types 1 and 3. However, in SCA6 and other dominantly inherited neurodegenerative disorders, RNAi-based strategies that selectively suppress expression of mutant alleles may be required. Using a Ca(V)2.1 mini-gene reporter system, we found that pathogenic CAG expansions in Ca(V)2.1 enhance splicing activity at the 3'end of the transcript, leading to a CAG repeat length-dependent increase in the levels of a polyQ-encoding Ca(V)2.1 mRNA splice isoform and the resultant disease protein. Taking advantage of this molecular phenomenon, we developed a novel splice isoform-specific (SIS)-RNAi strategy that selectively targets the polyQ-encoding Ca(V)2.1 splice variant. Selective suppression of transiently expressed and endogenous polyQ-encoding Ca(V)2.1 splice variants was achieved in a variety of cell-based models including a human neuronal cell line, using a new artificial miRNA-like delivery system. Moreover, the efficacy of gene silencing correlated with effective intracellular recognition and processing of SIS-RNAi miRNA mimics. These results lend support to the preclinical development of SIS-RNAi as a potential therapy for SCA6 and other dominantly inherited diseases.
Indexed as
Identifiers
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.