HEAT-KILLED <EM>ENTEROCOCCUS FAECIUM</EM>–DERIVED POLYDEOXYRIBONUCLEOTIDES ATTENUATE NEUROINFLAMMATION

Neuro-oxidative stress mediated by reactive oxygen and nitrogen species has been widely implicated in the pathogenesis of Parkinson's disease (PD). Polydeoxyribonucleotide (PDRN), a DNA-derived biopolymer with reported anti-inflammatory properties, has not been fully explored in the context of PD. In this study, PDRN purified from heat-inactivated Enterococcus faecium FBL1 (HEF PDRN) was structurally characterized by electrophoresis and Fourier transform infrared spectroscopy. Its cytoprotective effects were evaluated in MPTP induced SH-SY5Y and C2C12 cells, and its in vivo effects were examined in an MPTP-induced PD mouse model using behavioral assays, histological analysis, transcriptomics, and molecular profiling. HEF PDRN treatment was associated with improved motor performance in rotarod, grip strength, and wire-hanging tests, as well as reduced immobility in the forced swim test. Histological and immunohistochemical analyses indicated attenuation of MPTP-induced muscle damage, preservation of dopaminergic neurons, and reduced α-synuclein aggregation. Transcriptomic analysis revealed attenuation of MPTP-induced suppression of neuroprotective (Park7, and Sqstm1), myogenic (Myf5, MyoG, and Myh1), and osteogenic-associated (Bmp2, Runx2, and Wnt5b) gene expression, with enrichment of Wnt/β-catenin and BMP/SMAD signaling pathways. These effects were accompanied by modulation of MAPK signaling and activation of the adenosine A2A receptor, together with changes in β-catenin levels. Overall, HEF PDRN may represent a food fermentation–derived bioactive compound associated with antioxidant and anti-inflammatory signaling responses, along with modulation of MAPK mediated BMP/SMAD/Wnt pathways, under neuro-oxidative stress. These findings suggest its potential relevance for the development of functional food ingredients targeting neuroprotective and neuro muscular associated responses within an acute neurotoxicity model.