Harnessing Nanozyme Catalytic Activities for Multi-Target Intervention in Neurodegenerative Pathology

The therapeutic landscape for neurodegenerative diseases (NDs), including Alzheimer’s and Parkinson’s disease, remains challenging due to their complex, multifactorial pathogenesis and the limited efficacy of conventional therapies that primarily offer symptomatic relief. The emergence of nanozymes, nanomaterials with intrinsic enzyme-mimicking activities, presents a promising opportunity for multi-targeted intervention. This review comprehensively explores the rational design and therapeutic mechanisms of nanozymes in combating core pathological features of NDs, such as oxidative stress, protein aggregation, and neuroinflammation. We critically assess their remarkable ability to cross the blood–brain barrier and execute synergistic functions, including reactive oxygen species scavenging, misfolded protein degradation, and modulation of microglial activation. Furthermore, we provide a detailed analysis of the application and efficacy of nanozymes across major NDs, alongside a discussion on pharmacokinetics, biosafety, and prevailing challenges. By delineating the structure-enzyme-mimicking activity relationships and cellular-level mechanisms, this review aims to establish a foundational framework for the future development of nanozyme-based neuroprotective strategies, supporting ongoing efforts toward disease-modifying interventions for NDs.