The University of Osaka · Neuroscience
Professor Masayuki Nakamori's research lab focuses on the molecular mechanisms underlying myotonic dystrophy, particularly the role of RNA toxicity and alternative splicing dysregulation in disease pathogenesis. The lab investigates how expanded (CUG/CCUG) repeat mutations lead to widespread splicing defects, muscle wasting, and systemic complications in DM1 and DM2. Key research directions include identifying splicing biomarkers for disease severity, exploring the impact of transcription on repeat instability, and evaluating repurposed drugs like erythromycin as potential therapeutics. The lab also examines signaling pathways such as IL-6 and dystrophin splicing alterations that contribute to muscle immaturity and degeneration in congenital and adult-onset forms of the disease.
Figures are computed from collected data and may differ slightly.
Alternative splicing changes in skeletal muscle may serve as biomarkers of disease severity and therapeutic response in myotonic dystrophy.
More than 12 neurogenetic disorders are caused by unstable expansions of (CTG)•(CAG) repeats. The expanded repeats are unstable in germline and somatic cells, with potential consequences for disease severity. Previous studies have shown that contractions of (CAG)(95) are more frequent when the repeat tract is transcribed. Here we determined whether transcription can promote repeat expansion, using (CTG)•(CAG) repeat tracts in the size range that is typical for myotonic dystrophy type 1. We deriv
Oral erythromycin treatment, which has been widely used in humans with excellent tolerability, may be a promising therapy for DM1.
Myotonic dystrophy types 1 (DM1) and 2 (DM2) are dominantly inherited neuromuscular disorders caused by a toxic gain of function of expanded CUG and CCUG repeats, respectively. Although both disorders are clinically similar, congenital myotonic dystrophy (CDM), a severe DM form, is found only in DM1. CDM is also characterized by muscle fiber immaturity not observed in adult DM, suggesting specific pathological mechanisms. Here, we revealed upregulation of the interleukin-6 (IL-6) myokine signali
Alternative splicing of alpha-dystrobrevin is dysregulated in myotonic dystrophy type 1 (DM1) muscle, resulting in changes in alpha-syntrophin binding. These results raise the possibility that effects on alpha-dystrobrevin splicing may influence signaling in DM1 muscle cells.
Myotonic dystrophy type1 (DM1) is a multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant mRNA splicing of several genes has been reported to contribute to some of the symptoms, including myotonia and insulin resistance, but the cause of muscle wasting is unknown. Dystrophin is a cytoskeletal protein that is required for structural stability and signaling at the sarcolemma and has several spliced isoforms. We investigated the alternative splicing of dystrophin in ske
Muscular dystrophies are a group of diseases that primarily affect striated muscle and are characterized by the progressive loss of muscle strength and integrity. Major forms of muscular dystrophies are caused by the abnormalities of the dystrophin glycoprotein complex (DGC) that plays crucial roles as a structural unit and scaffolds for signaling molecules at the sarcolemma. α-Dystrobrevin is a component of the DGC and directly associates with dystrophin. α-Dystrobrevin also binds to intermedia
Dentatorubral-pallidoluysian atrophy (DRPLA) is a devastating genetic disease presenting myoclonus, epilepsy, ataxia, and dementia. DRPLA is caused by the expansion of a CAG repeat in the ATN1 gene. Aggregation of the polyglutamine-expanded ATN1 protein causes neuro-degeneration of the dentatorubral and pallidoluysian systems. The expanded CAG repeats are unstable, and ongoing repeat expansions contribute to disease onset, progression, and severity. Inducing contractions of expanded repeats can
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