A Systematic Review Focusing on the Link between Engineered Nanoparticles and Neurodegeneration

Engineered nanoparticles (ENPs) have widely revolutionized many fields, including medicine, technology, environmental science, and industry. However, with the wide use of ENPs in everyday life, concerns are increasingly being raised about their potential neurotoxic effects on the central nervous system (CNS), particularly in relation to neurodegeneration and neuroinflammation. The present systematic review focuses on reporting the current knowledge about the neurotoxic potential of ENPs, with particular attention to their mechanism of action in neuroinflammation and neurodegeneration. This PRISMA based systematic review encompassed studies from Pubmed, Embase, and Web of Science. Eligibility criteria included focusing on engineered NPs and their impacts on neuroinflammation, neurodegeneration, and neurotoxicity. Evidence shows that ENPs easily can cross the blood-brain barrier (BBB) inducing neuronal damage and neurotoxicity due to oxidative stress, inflammation, mitochondrial dysfunction, and cell death. Inflammation plays a crucial role in activating glial cells, such as microglia and astrocytes, leading to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS). This increases the vulnerability of the brain to systemic inflammation. In conclusion, as ENP exposure continues to increase, understanding their long-term effects on the brain is fundamental to developing effective strategies to mitigate their impact on neuronal human health. © 2025 American Chemical Society.