Neuroprotective effects of Agaricus bisporus protein extract in MPTP-induced Parkinson's disease: modulation of oxidative stress, neuroinflammation, and apoptotic pathways in the Substantia Nigra.

BACKGROUND

Agaricus bisporus contains bioactive proteins, including tyrosinase, which may influence dopaminergic metabolism. Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons driven by oxidative stress, neuroinflammation, and apoptosis.

OBJECTIVE

To evaluate the neuroprotective effects of an Agaricus bisporus protein extract (ABE) and its mechanistic basis in an MPTP-induced mouse model of PD.

METHODS

A tyrosinase-enriched protein fraction was isolated and administered orally to MPTP-treated mice for 20 days. Behavioral performance, dopaminergic markers, oxidative stress parameters, inflammatory mediators, and apoptosis-related proteins were assessed in the substantia nigra.

RESULTS

ABE exhibited preserved tyrosinase activity after simulated gastrointestinal digestion. In vivo, ABE increased plasma L-DOPA and dopamine levels by ∼55% and ∼30%, respectively (p < 0.001 and p < 0.01), and significantly elevated nigral dopamine (p < 0.001) and AADC activity (p < 0.01). Motor deficits were attenuated, with reduced beam-walking errors (p < 0.001). Oxidative stress was mitigated, as evidenced by restoration of SOD and CAT activities (p < 0.001) and reduction of MDA, H₂O₂, and NO levels (p < 0.05). ABE suppressed neuroinflammation by decreasing NF-κB p65 expression (p < 0.001) and reducing IL-6, IL-1β, and TNF-α levels (p < 0.05). Apoptotic signaling was shifted toward cell survival, with increased Bcl-2 (p < 0.01) and decreased Bax and Bad expression (p < 0.01). Immunohistochemistry confirmed preservation of tyrosine hydroxylase - positive neurons (p < 0.001).

CONCLUSION

ABE exerts neuroprotective effects in MPTP-induced PD via tyrosinase-associated enhancement of dopaminergic metabolism, alongside antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.