Objective: This study aims to evaluate the neuroprotective potential of various mushroom extracts in in vitro models of PD.

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. A hallmark of PD pathology is the presence of Lewy bodies—intracellular aggregates primarily composed of misfolded α-synuclein protein. Increasing evidence highlights mushrooms as rich sources of bioactive compounds, including phenols, flavonoids, polysaccharides, vitamins, carotenoids, ergothioneine, and pentacyclic triterpenes. These compounds exhibit potent antioxidative and anti-inflammatory properties, positioning mushrooms as promising candidates for neuroprotection.

Method: Fifty mushroom extracts were prepared using water/ethanol extraction and screened for neuroprotective properties in primary cortical neurons and SH-SY5Y cells. PD-like pathology was induced by α-synuclein fibril inclusion formation and exposure to the neurotoxins MPP⁺ and 6-OHDA. Cells were pre-treated with different extract concentrations (1, 5, 10, 25, and 50 µg/mL) prior to toxin exposure. Cell viability was assessed using MTT, Alamar Blue, and LDH assays. Mitochondrial integrity and α-synuclein aggregation were examined via immunocytochemistry, while apoptotic markers (cytochrome c release and cleaved caspase-3) were analyzed through Western blot. Statistical analyses were performed using one-way ANOVA

Results: Specific mushroom extracts demonstrated a dose-dependent increase in cell viability, mitigated mitochondrial fragmentation, and reduced oxidative stress. Additionally, pre-treatment with select extracts significantly attenuated cytochrome c release and apoptosis in PD models. These findings suggest that certain mushroom extracts exert neuroprotective effects by modulating oxidative stress, mitochondrial dysfunction, and α-synuclein aggregation.

Conclusion: This study provides compelling evidence supporting the neuroprotective properties of medicinal mushroom extracts in PD pathology. The results highlight their potential as novel therapeutic agents targeting key pathogenic mechanisms, including oxidative stress, neuroinflammation, and protein aggregation. Further research is warranted to explore their clinical applications in PD treatment.

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