Bifunctional\nInhibitor Lentinan Inhibits Fibrillogenesis\nof Amyloid‑β Protein and α‑Synuclein and\nAlleviates Their Cytotoxicity: In Vitro and In Vivo Studies

Alzheimer’s disease (AD) and Parkinson’s\ndisease\n(PD) are the two most common neurodegenerative diseases in the world.\nMisfolding of β-amyloid (Aβ) and α-synuclein (α-syn)\nand subsequent fibril formation are closely associated with the pathogenesis\nof AD and PD, respectively. Lentinan is a natural product commonly\nused in medicine and dietary supplements. It has potential antitumor,\nanti-inflammatory, and antiviral effects, but the underlying mechanism\nof its action on AD and PD remains unclear. In this study, lentinan\ninhibited the formation of Aβ and α-syn fibers in a dose-dependent\nmanner and disrupted their mature fibers. Lentinan inhibited the conversion\nof Aβ and α-syn conformations to β-sheet-rich conformations.\nAdditionally, lentinan protected Caenorhabditis elegans against damage caused by the accumulation of Aβ and α-syn\naggregation and prolonged their lifespan. Notably, the beneficial\neffects of lentinan in AD and PD mice were also demonstrated, including\nameliorating the cognitive and memory impairments in AD mice and behavioral\ndeficits in PD mice. Finally, molecular interactions between lentinan\nand Aβ/α-syn pentamers were also explored using molecular\ndocking.