RNA-seq analysis of alpha-synucleinopathy mouse models with nanozyme treatment
Alpha-synucleinopathies, including Parkinson's disease and related disorders, are characterized by progressive neurodegeneration associated with protein aggregation and neuroinflammation. Although oxidative stress has been widely implicated in disease progression, the role of nitrative stress and reactive nitrogen species (RNS) in modulating alpha-synuclein pathology remains incompletely understood.In this study, we investigated the mechanistic contribution of redox imbalance to alpha-synuclein-driven neurodegeneration using engineered iridium-based nanozymes with distinct catalytic properties. Specifically, a copper-tuned Ir3Cu nanozyme that promotes nitric oxide derived RNS generation was compared with a copper-free iridium nanozyme with broad reactive oxygen and nitrogen species scavenging activity.To define transcriptional changes associated with disease progression and nanozyme-mediated modulation, bulk RNA sequencing was performed on brain tissues collected from mouse models of alpha-synucleinopathy under multiple experimental conditions, including vehicle treated controls, iridium nanozyme treatment, and Ir3Cu nanozyme exposure. These models included preformed fibril (PFF)-induced alpha-synuclein pathology, enabling the assessment of neurodegenerative and neuroinflammatory responses in vivo.RNA sequencing data were analyzed to identify differentially expressed genes and pathways associated with nitrative stress, immune activation, and neurodegeneration. Particular focus was placed on pathways related to nitric oxide signaling, inducible nitric oxide synthase (iNOS), and downstream molecular events linked to DNA damage and PARP1 activation.These data provide a comprehensive resource for understanding the transcriptional programs underlying alpha-synuclein pathology and establish nitrative stress as a key driver of neurodegenerative processes. Furthermore, this dataset offers insights into how redox-modulating nanomaterials influence neuroinflammation and disease progression, providing a foundation for the development of therapeutic strategies targeting reactive nitrogen species in neurodegenerative disorders.