Neuroprotective Mushrooms

Abstract

Alternative medicines commonly supplement or, at times, replace standard medical treatment. One area of increasing attention is disease-modifying medicines for neurodegenerative diseases. However, few such alternatives have been investigated thoroughly with an eye toward understanding mechanisms of action for clinical use. Medicinal mushrooms have important health benefits and pharmacological activities with anti-inflammatory, antioxidant, antibacterial, antiviral, immunomodulatory, digestive, cytoprotective, homeostatic, and neuroprotective activities. Edible mushrooms are known to play roles in preventing age-related diseases. Several studies have revealed that polysaccharides, terpenes, and phenolic compounds are chemical components derived from mushrooms with pharmacological activities. Due to limited effective protocols for mushroom protein extraction for proteomic studies, information about these medicinally related proteins and their biological functions remains enigmatic. Herein, we have performed proteomic studies of two mushroom species Laricifomes officinalis (agarikon) and Grifola frondosa (maitake). These studies serve to uncover a foundation for putative proteome-associated neuroprotective processes. The recovered proteins from both species show multiple cell-specific signaling pathways including unfolded protein response, and mitochondrial protein import as well as those linked to BAG2, ubiquitination, apoptosis, microautophagy, glycolysis, SNARE, and immunogenic cell signaling pathways. This study uncovered mushroom proteome-associated proteins which serve to better understand the structural and functional properties of mushrooms used as alternative medicines for broad potential health benefits.

Keywords: agarikon; maitake; mushroom; neuroprotection; proteome.

Figure 1.. Pathway enrichment of differentially expressed unique proteins in agarikon and maitake mushrooms.

Gene ontology (GO)-term functional enrichment by 5 categories (immune response, biological process, cellular component, KEGG, and Reactome) performed using Cytoscape in conjunction with the plug-in ClueGO. Enriched signaling pathways of unique proteins for (A) agarikon and (B) maitake.

Figure 2.. Differential proteomic analysis of agarikon and maitake common proteins.

(A) Principal component analysis (PCA) showing the three top components used for proteomic analysis. (B) Volcano plot showing the fold change plotted against the p value highlighting significantly changed proteins in maitake compared to agarikon. Red – upregulation and green –downregulation; p ≤ 0.05 and an absolute fold change ≥ 2. (C) Heatmap showing hierarchical clustering of agarikon and maitake FDR-adjusted proteins. Red – upregulation and green – downregulation. Abbreviations: Sample_A; agarikon, sample_M; maitake.

Figure 3.. Pathway enrichment of differentially expressed common proteins in agarikon and maitake mushrooms.

Canonical pathway enrichment analysis of maitake proteome compared to agarikon proteome was performed using IPA (Qiagen). Orange color (activation of pathway), blue color (inhibition of pathway), and grey color (no activity pattern of pathway). The p value ≤ 0.05.

Figure 4.. Pathway enrichment of up- and down-regulated common proteins in agarikon and maitake mushrooms.

Enriched signaling pathways of common mushroom proteins that were (A) upregulated or (B) downregulated. Gene ontology (GO)-term functional enrichment by 5 categories (immune response, biological process, cellular component, KEGG, and Reactome) performed using Cytoscape in conjunction with the plug-in ClueGO.