Progress in precision drug delivery systems for neurodegenerative diseases with muscle atrophy

Neurodegenerative diseases frequently co-occur with skeletal muscle atrophy, creating a complex comorbid condition that significantly accelerates functional decline and increases mortality. This dual pathology is driven by interconnected mechanisms such as protein aggregation, neuroinflammation, and impaired axonal transport, disrupting critical neuromuscular junctions (NMJs). However, a significant research gap exists in the development of therapeutic strategies that can effectively and simultaneously target both the central nervous system (CNS) and peripheral muscle tissues. We systematically summarizes the core pathological targets and critically evaluates recent advances in precision drug delivery systems designed to overcome these challenges. We explore innovative strategies, including engineered viral vectors and receptor-targeted nanoparticles for CNS delivery, as well as smart biomaterials and extracellular vesicles (EVs) for muscle-specific and dual-organ intervention, highlighting the growing role of artificial intelligence (AI) in optimizing their design. Furthermore, this review discusses the construction of multidimensional efficacy evaluation systems that integrate behavioral, molecular, and imaging biomarkers and addresses pivotal clinical translation challenges, from scalable production to species-specific differences. By examining the pathological landscape across the central nervous system and skeletal muscle together, this review connects mechanisms that have more often been considered in isolation and evaluates how their convergence may inform the design of delivery strategies targeting both tissue compartments.