Objective: This study aimed to evaluate the neuroprotective potential of various mushroom extracts across four distinct cellular models of PD. Furthermore, we sought to identify a lead candidate capable of modulating key pathogenic mechanisms and exhibiting broad-spectrum efficacy against four neurotoxic challenges: α-synuclein preformed fibrils (PFFs), 6-OHDA, MPP+, and rotenone.

Background: Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein aggregates (Lewy bodies). Increasing evidence suggests that medicinal mushrooms are rich sources of bioactive compounds—including phenols, polysaccharides, and ergothioneine—that possess potent anti-inflammatory and antioxidative properties. Consequently, these extracts represent promising candidates for neuroprotective interventions.

Method: Over 40 mushroom extracts were prepared via water/ethanol extraction and screened for neuroprotection in mouse primary cortical neurons and SH-SY5Y cells. PD-like pathology was induced using α-synuclein PFFs and three neurotoxins (MPP+, 6-OHDA, and rotenone). Cell viability was assessed via MTT, Alamar Blue, and LDH assays. Mitochondrial integrity and α-synuclein aggregation were evaluated using immunocytochemistry, while apoptosis markers (cytochrome c, cleaved caspase-3) were analyzed via Western blotting.

Results: A subset of mushroom extracts significantly improved cell viability in a dose-dependent manner (p < 0.05) and preserved mitochondrial morphology compared to toxin-only controls. These extracts effectively attenuated intracellular α-synuclein accumulation and reduced markers of oxidative stress. The observed protective effects were consistent across biological replicates and experimental models. Notably, a single lead candidate exhibiting robust, broad-spectrum efficacy against all four neurotoxic challenges was identified.

Conclusion: These findings demonstrate the multi-target neuroprotective potential of specific mushroom extracts against PD-associated pathology. This study provides a strong foundation for the development of novel, naturally derived therapeutics targeting neuroinflammation, oxidative stress, and α-synuclein aggregation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/screening-the-neuroprotective-potential-of-mushroom-extracts-in-in-vitro-models-of-parkinsons-disease/