Skeletal muscle atrophy emerges from intertwined neuromuscular and metabolic failures, in which neuromuscular junction destabilization, excitation contraction coupling defects, and mitochondrial dysfunction collectively intensify calcium dysregulation and drive the accumulation of reactive oxygen and nitrogen species (RONS), reinforcing proteolytic and catabolic signaling programs. To integrate recent evidence on the neuromuscular redox interface and highlight therapeutic strategies that target these interdependent drivers of atrophy. RONS-mediated activation of NF-κB and FOXO pathways accelerates ubiquitin proteasome and autophagy lysosome degradation, leading to motor unit loss. Stem cell therapies (satellite cells, MSCs, and iPSC progenitors) seek to restore regenerative potential but face hurdles in engraftment and reinnervation. Gene-based interventions, including antioxidant gene delivery, Nrf2 activation, RNA modulators, and CRISPR editing, offer new avenues but remain limited by safety and delivery barriers. Bioengineering platforms such as hydrogels, decellularized scaffolds, and extracellular vesicles provide architectural, trophic, and immunomodulatory support. Translational progress requires rigorous safety pipelines, mechanistic biomarkers of motor unit recovery, and modular combination regimens that integrate cells, genes, scaffolds, and rehabilitative input. By aligning neuromuscular biology with redox control, emerging strategies hold promise to rebuild innervated, fatigue-resistant muscle across acquired and genetic atrophy syndromes.

Background: Trehalose is a promising therapeutic candidate for Alzheimer’s disease (AD) that is known to induce autophagy and facilitate misfolded proteins clearance such as amyloid-β and hyperphosphorylated tau. Despite there is emerging evidence that trehalose has a wider range of molecular mechanisms and thus has a greater neuroprotective profile. Objective: To summarize the emerging molecular mechanisms underlying the neuroprotective effects of trehalose beyond classical autophagy and discuss its therapeutic potential in AD. Methods: Published evidence from preclinical studies including in-vitro and in-vivo models, along with hypothetical and emerging findings from early clinical investigations was reviewed to evaluate the molecular mechanisms, therapeutic effects, and translational challenges associated with trehalose in AD. Results: In addition to classical autophagy signalling, recent studies have demonstrated that autophagy can also regulate the stability of neuronal membrane microdomains, prevent lipid bilayers disruption by amyloid proteins, and regulate stress granules dynamics that affect the function of RNA-binding proteins. Other discoveries indicate that interactions with nutrient-sensing pathways and glucose transporter systems that simulate metabolic stress, which may activate protective mechanisms separate from the inhibition of mTOR. Trehalose could also involve in lysosomal-autophagosome fusion and modulate the microglia and astrocytes activation, suggesting an important immunometabolic function. Trehalose often connects to the gut-brain axis and show their effect in gut microbiota composition, microbial metabolite signalling and gut barrier function. These effects can influence systemic inflammation, availability of short-chain fatty acids, bile acid profiles and vagus-mediated gut-to-brain communication, all of which can influence neuroinflammation networks in AD. Conclusion: Although promising results have been reported, primarily from preclinical studies, with early human investigations now beginning to emerge, opportunities remain to address, such as poor oral bioavailability, penetration into the brain and long-term safety in elderly patients. Mechanistic dissection in multi-omics approaches, microbiome-stratified models and early-phase clinical testing are the areas that need to be targeted in future research. A broader understanding of the mechanisms of action of trehalose provides a good chance to reimagine its therapeutic implications and develop novel approaches to AD.