Altered Purkinje cell miRNA expression and SCA1 pathogenesis

Rodríguez-Lebrón, Edgardo; Liu, Gumei; Keiser, Megan S.; Behlke, Mark A.; Davidson, Beverly L.

doi:10.1016/j.nbd.2013.01.019

Cited by 39 publications

(44 citation statements)

References 39 publications

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“…We think this is improbable, however, as we used miS1 in an older vector platform and reversed aberrant miRNA expression in the B05 model. 29 A third possibility is that the high capsid dose is toxic. Testing for this could be done using empty capsid preparations as controls at the doses evaluated here.…”

Section: Discussionmentioning

confidence: 99%

RNAi prevents and reverses phenotypes induced by mutant human ataxin‐1

Keiser

Monteys

Corbau

et al. 2016

Annals of Neurology

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Objective Spinocerebellar ataxia type 1 is an autosomal dominant fatal neurodegenerative disease caused by a polyglutamine expansion in the coding region of ATXN1. We showed previously that partial suppression of mutant ataxin-1 (ATXN1) expression, using virally-expressed RNAi triggers, could prevent disease symptoms in a transgenic mouse model and a knock in mouse model of the disease, using a single dose of virus. Here, we set out to test if RNAi triggers targeting ATXN1 could not only prevent, but also reverse disease readouts when delivered after symptom onset. Methods We administered recombinant adeno-associated virus (rAAV) expressing miS1, an artificial miRNA targeting human ATXN1 mRNA (rAAV.miS1) to a mouse model of SCA1 (B05 mice). Viruses were delivered prior to or after symptom onset at multiple doses. Control B05 mice were treated with rAAVs expressing a control artificial miRNA, or with saline. Animal behavior, molecular phenotypes, neuropathology and magnetic resonance spectroscopy were done on all groups and data were compared to wildtype littermates. Results We found that SCA1 phenotypes could be reversed by partial suppression of human mutant ATXN1 mRNA by rAAV.miS1 when delivered after symptom onset. We also identified the therapeutic range of rAAV.miS1 that could prevent or reverse disease readouts. Interpretation SCA1 disease may be reversible by RNAi therapy, and the doses required for advancing this therapy to humans are delineated.

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Section: Discussionmentioning

confidence: 99%

RNAi prevents and reverses phenotypes induced by mutant human ataxin‐1

Keiser

Monteys

Corbau

et al. 2016

Annals of Neurology

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“…The R4/B family are the smallest RGS proteins in size having only a short peptide sequence surrounding the RGS box with the exception of RGS3 (Blazer et al, 2011;Calipari et al, 2014;Monroy et al, 2013b;Rodriguez-Lebron et al, 2013;Sethakorn and Dulin, 2013;Villasenor et al, 2010). Increased expression of RGS8 was shown to ironically have an increase on G-protein-gated potassium channel kinetics (Saitoh et al, 1997).…”

Section: Rgs8mentioning

confidence: 99%

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

Woodard

Jardín

Berna‐Erro

et al. 2015

International Review of Cell and Molecular Biology

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“…Interaction between miR-150-5p and VEGFA was previously reported [36], and PDGFB mRNA has 3′ untranslated region that could interact with miR-150-5p (Targetscan database). In an attempt to show some evidence of the interactions between miR-150-5p and PDGFB, we measured the serum concentration of PDGF-BB.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Serum microRNAs in Autoimmune Pancreatitis

et al. 2015

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Background/Aims: Autoimmune pancreatitis (AIP) is a rare disease that has recently emerged as a unique type of pancreatitis with a presumed autoimmune etiology. MicroRNA (miRNA) is a small non-coding RNA that targets multiple mRNAs. miRNAs might exist in serum in a stabilized form, suggesting its potential application as a biomarker. We here examined the miRNA expression profile in the serum of patients with AIP. Methods: miRNAs were prepared from serum samples of patients with various pancreatic diseases (AIP (n = 3, each before and after the steroid therapy), chronic pancreatitis (n = 5), pancreatic cancer (n = 5)) or healthy controls (n = 5). A human miRNA Oligo chip containing approximately 2,000 miRNAs was used to identify differentially expressed miRNAs. Ingenuity Pathway Analysis (IPA) was used for the integrated analysis of altered miRNAs. Results: Microarray analysis identified miRNAs highly expressed in the serum of patients with AIP: 13 miRNAs vs. CP, 204 miRNAs vs. pancreatic cancer, and 19 miRNAs vs. healthy controls. miR-150-5p was commonly upregulated in AIP compared to the other samples. IPA revealed the most biological processes affected by the steroid therapy including cellular development, cellular growth, and cell movement. Conclusion: Our results identified that miRNAs were differentially expressed in the serum of AIP patients.

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Altered Purkinje cell miRNA expression and SCA1 pathogenesis

Cited by 39 publications

References 39 publications

RNAi prevents and reverses phenotypes induced by mutant human ataxin‐1

RNAi prevents and reverses phenotypes induced by mutant human ataxin‐1

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

Comprehensive Analysis of Serum microRNAs in Autoimmune Pancreatitis

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