Zhang_2025_Int.J.Biol.Macromol_304_140758

Alzheimer's disease (AD) is predominantly characterized by cholinergic dysfunction, mitochondrial impairment, oxidative stress, and inflammation, primarily driven by amyloid-beta (Abeta) peptides. This study investigates the protective effects of Lycium ruthenicum Murray-derived exosome-like nanoparticles (LELN) in AD models using transgenic Caenorhabditis elegans (C. elegans). Findings showed that C. elegans effectively internalized LELN, which remained stable in vivo. Compared with untreated controls, treatment with 600 microg/mL LELN significantly extended the lifespan of CL4176 [myo-3p::Abeta(1-42)] and CL2006 [unc-54/Abeta(1-42)] worms by 34.78 % and 34.85 %, respectively, and delayed Abeta-induced paralysis by 52.42 % and 42.72 %, respectively. Furthermore, LELN increased the chemotaxis index of CL2355 [snb-1::Abeta(1-42)] worms from 11.11 % to 55.56 %. Mechanistically, LELN reduced the levels of Abeta oligomers and monomers via the DAF-16 pathway, consequently alleviating AD-like symptoms in transgenic C. elegans. The effects of LELN include inhibiting acetylcholinesterase activity to mitigate cholinergic dysfunction, restoring mitochondrial membrane potential and adenosine triphosphate production to ameliorate mitochondrial dysfunction, and reducing oxidative stress and inflammation. Collectively, these results highlight the protective role of LELN against Abeta-induced AD pathology and underscore their potential as a therapeutic candidate for AD treatment.