Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Pharmacological inhibition of HDAC6 downregulates TGF-β via Smad2/3 acetylation and improves dystrophin-deficient muscles. Abstract / SummaryThe absence of dystrophin in Duchenne muscular dystrophy (DMD) disrupts the dystrophin dystroglycan glycoprotein complex (DGC) resulting in fibers fragility and atrophy, associated with fibrosis and microtubules and neuromuscular junction (NMJ) disorganization. The specific non-conventional cytoplasmic histone deacetylase 6 (HDAC6) was previously shown to regulate acetylcholine receptor distribution and muscle atrophy. Here we show that administration of the HDAC6 specific inhibitor tubastatin A to the DMD mouse model mdx improves muscle strength, restores microtubules, NMJ and DGC organization, and reduces muscle atrophy and fibrosis. These effects involve the known action of HDAC6 on microtubules acetylation and muscle atrophy but also involve a yet undiscovered action of HDAC6 on transforming growth factor beta (TGF-{beta}) signaling. Conversely, to inhibitors of nuclear HDACs that regulate TGF-{beta} signaling via the activation of Follistatin expression, HDAC6 inhibition acts downstream of TGF-{beta} ligands and receptors by increasing Smad2/3 acetylation in the cytoplasm which in turn inhibits its phosphorylation and transcriptional activity.
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The categories of this paper are: neuroscience
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The categories of this paper are: cancer
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The categories of this paper are: biophysics
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The categories of this paper are: cognition
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The categories of this paper are: evolutionary
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The categories of this paper are: bioinformatics
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The categories of this paper are: behavior
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The categories of this paper are: plant
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The categories of this paper are: pathology
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The categories of this paper are: systems
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The categories of this paper are: animal
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The categories of this paper are: cell
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The categories of this paper are: scientific
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The categories of this paper are: ecology
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The categories of this paper are: paleontology
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The categories of this paper are: synthetic