Pyran compound 7r exerts neuroprotective effects against Parkinson’s disease via modulating oxidative stress and autophagy

Aberrant aggregation of α-synuclein (α-syn) represents a key pathological hallmark of Parkinson's disease (PD), with oxidative stress and defective autophagy driving disease progression. In this study, the neuroprotective effects of pyran compound 7r (NP7r) were evaluated in Caenorhabditis elegans models of PD. Treatment with 10 μM NP7r significantly decreased mitochondrial reactive oxygen species levels in the NL5901 strain and alleviated 6-hydroxydopamine-induced dopaminergic neuronal degeneration in the BZ555 strain. Mechanistically, NP7r mitigated oxidative stress by upregulating skn-1 and antioxidant genes, including gst-4 and gcs-1 . Furthermore, NP7r reduced α-syn aggregation by enhancing autophagy-related genes unc-51 and lgg-1 , thereby promoting aggrephagy. This effect was accompanied by prominent upregulation of CCT family genes, among which cct-6 exhibited the most significant induction. Collectively, these results demonstrate that NP7r confers neuroprotection in C. elegans PD models via modulating oxidative stress and autophagy pathways, highlighting its potential as a promising lead compound for PD therapy.