Dystrophin is a protein crucial for maintaining the structural integrity of skeletal muscle. So far, the attention was focused on the role of dystrophin in muscle in view of the devastating progression of weakness and early death that characterises Duchenne muscular dystrophy. However, in the last few years, the role of shorter dystrophin isoforms, including development and adult expression-specific mechanisms, has been a greater focus. Within the cerebral landscape, various cell types, such as glia, oligodendrocytes, Purkinje cells, cerebellar granule cells, and vascular-associated cells express a spectrum of dystrophin isoforms, including Dp427, Dp140, Dp71, and Dp40. The interaction of these isoforms with a multitude of proteins, suggests their involvement in neurotransmission, influencing several circuit functions. This review presents the intricate interactions among dystrophin isoforms and diverse protein complexes across different cell types and brain regions, and the associated clinical complications. We focus on studies investigating protein interactions with dystrophin in the past 30 years, at a biochemical level. In essence, brain's dystrophin landscape is a thrilling exploration of diversity, challenging preconceptions and opening new avenues for understanding the central nervous system physiology. It also holds potential therapeutic implications for neurological complications in which brain dystrophin deficiency is involved. By revealing the molecular complexities related to dystrophin, this review paves the way for future investigations and therapeutic interventions for this central nervous system aspect of Duchenne muscular dystrophy.
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http://dx.doi.org/10.1093/brain/awae384 | DOI Listing |
Brain
December 2024
Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Dystrophin is a protein crucial for maintaining the structural integrity of skeletal muscle. So far, the attention was focused on the role of dystrophin in muscle in view of the devastating progression of weakness and early death that characterises Duchenne muscular dystrophy. However, in the last few years, the role of shorter dystrophin isoforms, including development and adult expression-specific mechanisms, has been a greater focus.
View Article and Find Full Text PDFJ Biol Chem
November 2024
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. Electronic address:
Duchenne muscular dystrophy (DMD) gene encodes dystrophin, a large multidomain protein. Its nonfunctionality leads to dystrophinopathies like DMD and Becker muscular dystrophy, for which no cure is yet available. A few therapies targeted towards specific mutations can extend the lifespan of patients, although with limited efficacy and high costs, emphasizing the need for more general treatments.
View Article and Find Full Text PDFEMBO Rep
November 2024
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135, Porto, Portugal.
Cytokinesis physically separates daughter cells at the end of cell division. This step is particularly challenging for epithelial cells, which are connected to their neighbors and to the extracellular matrix by transmembrane protein complexes. To systematically evaluate the impact of the cell adhesion machinery on epithelial cytokinesis efficiency, we performed an RNAi-based modifier screen in the Drosophila follicular epithelium.
View Article and Find Full Text PDFNeuromuscul Disord
November 2024
Department of Paediatric Neurology, Catholic University, Rome, Italy. Electronic address:
Biochim Biophys Acta Proteins Proteom
January 2025
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico. Electronic address:
Dystrophin Dp71 is essential for the development of the nervous system. Its alteration is associated with intellectual disability. Different Dp71 isoforms are generated by alternative splicing; however, their functions have not been fully described.
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