RT Journal Article ID 44ab31e9573a147f A1 Bennett, Louise A1 Sheean, Paul A1 Zabaras, Dimitrios A1 Head, Richard T1 Heat-Stable Components of Wood Ear Mushroom, Auricularia polytricha (Higher Basidiomycetes), Inhibit In Vitro Activity of Beta Secretase (BACE1) JF International Journal of Medicinal Mushrooms JO IJM YR 2013 FD 2013-04-26 VO 15 IS 3 SP 233 OP 249 K1 medicinal mushrooms K1 beta secretase K1 BACE1 K1 food processing K1 Maillard K1 Auricularia polytricha K1 Agaricus bisporus K1 Flammulina velutipes K1 Lentinus edodes AB The consumption of mushrooms has been linked with protection against dementia, including Alzheimer's disease (AD), by several biological pathways including inhibiting beta-site APP-cleaving enzyme (BACE1), which is responsible for releasing toxic β-amyloid peptide in the brain. We have investigated the capacity of several medicinal mushroom species−Auricularia polytricha (wood ear mushroom), Agaricus bisporus (button mushroom), Flammulina velutipes (winter or enoki mushroom), and Lentinus edodes (shiitake mushroom)−in the regulation of BACE1. Mushrooms were subjected to a generic food-compatible processing method to detect process-stable or process-modified products; the effects of processing were interpreted to infer the chemical classes associated with bioactivity. We have shown previously that in addition to enzyme inhibition, in the presence of the BACE1 proenzyme, heteropolymeric species such as heparin can activate BACE1 by modulating access to the catalytic site. We observed both inhibitory and activating components of the various mushrooms. Only BACE1 inhibitory species were detected in unprocessed and processed forms of A. polytricha, whereas the dominant extracted species from A. bisporus, F. velutipes, and L. edodese were activators of BACE1. It is not known whether activating species were masking the presence of inhibitory species in A. bisporus, F. velutipes, and L. edodes. Inhibitory species were attributed to hispidin-derived polyphenols, whereas activating species were attributed to soluble polysaccharides and possibly low-mass Maillard products produced during processing. Larger molecular BACE1-activating species are unlikely to be bioavailable to brain in contrast with possible brain bioavailability of smaller, lipophilic hispidins. PB Begell House LK https://www.dl.begellhouse.com/journals/708ae68d64b17c52,3a24b2df76f12ae0,44ab31e9573a147f.html