Molecular signatures of inherited and acquired sporadic late onset

Acquired sporadic late onset nemaline myopathy (SLONM) and inherited nemaline myopathy (iNM) both feature accumulation of nemaline rods in muscle fibers. Unlike iNM, SLONM is amenable to therapy. The distinction between these disorders is therefore crucial when the diagnosis remains ambiguous after initial investigations. We sought to identify biomarkers facilitating this distinction and to investigate the pathophysiology of nemaline rod formation in these different disorders. Twenty-two muscle samples from patients affected by SLONM or iNM underwent quantitative histological analysis, laser capture microdissection for proteomic analysis of nemaline rod areas and rod-free areas, and transcriptomic analysis. In all iNM samples, nemaline rods were found in subsarcolemmal or central aggregates, whereas they were diffusely distributed within muscle fibers in most SLONM samples. In SLONM, muscle fibers harboring nemaline rods were smaller than those without rods. Necrotic fibers, increased endomysial connective tissue, and atrophic fibers filled with nemaline rods were more common in SLONM. Proteomic analysis detected differentially expressed proteins between nemaline rod areas and rod-free areas, as well as between SLONM and iNM. These differentially expressed proteins implicated immune, structural, metabolic, and cellular processes in disease pathophysiology. Notably, immunoglobulin overexpression with accumulation in nemaline rod areas was detected in SLONM. Transcriptomic analysis corroborated proteomic findings and further revealed substantial gene expression differences between SLONM and iNM. Overall, we identified unique pathological and molecular signatures associated with SLONM and iNM, suggesting distinct underlying pathophysiological mechanisms. These findings represent a step towards enhanced diagnostic tools and towards development of treatments for SLONM.

News Core Center for Musculoskeletal Biology and Medicine

Molecular mechanisms underlying totipotency

Congenital myopathies in the adult neuromuscular clinic

Alzheimer's disease associated with Down syndrome: a genetic form

Frontiers Genetic and Epigenetic Interplay Define Disease Onset

Ferroptosis, Pyroptosis, and Cuproptosis in Alzheimer's Disease

Parkinson Disease: Translating Insights from Molecular Mechanisms

Proteomics of brain, CSF, and plasma identifies molecular

Modulation of Myosin Regulatory light chains (RLC) and Myosin

Molecular signatures of inherited and acquired sporadic late onset

Carcinogenesis: Mechanisms and Manifestations - Toxicologic Pathology

PDF) Molecular signatures of inherited and acquired sporadic late

Bone marrow-derived inducible microglia-like cells ameliorate

Cancers, Free Full-Text

Full article: To protect and modify double-stranded RNA – the