Mushroom-derived molecules show great potential for alleviating the pathological manifestations of Alzheimer’s disease in the elderly population. A scientific review published in Nutrients (Tong et al., 2023) provides an up-to-date account of research to date. (1)
1. Mushrooms against Alzheimer’s disease.
Alzheimer’s Disease
(AD) is characterized by a set of disorders related to the progressive dysfunction and death of neurons. Its global prevalence was estimated at 50 million in 2019 and is estimated to increase to 152 million by 2060 due to the increasing share of the elderly in the population. (2)
Most of the drugs available today are aimed at transient relief of symptoms rather than at the source of the disease. And research into new remedies identifies natural functional ingredients isolated from fungi as promising tools for treatment.
2. The mechanism of action
The therapeutic potential of various mushroom metabolites for neuroprotection, with particular emphasis on Alzheimer’s, is related to their large number of bioactive compounds, such as polysaccharides, phenols, and peptides.
The various mechanisms of action examined include antioxidant and antineuroinflammatory activity, inhibition of apoptosis, and stimulation of neurite outgrowth.
3. The bioactive substances of fungi
An estimated 140,000-160,000 species of fungi exist. The species studied so far represent only about 10 percent of them. Of these, about 700 were found to be beneficial in the treatment of diseases.
‘Many bioactivesubstances have been identified and purified from mushrooms, such as easily digestible proteins, carbohydrates, terpenes, vitamins, etc. Various mushroom metabolites also demonstrate potential neuroprotective properties’, the researchers explain.
3.1 Carbohydrates, polysaccharides
Carbohydrates-polysaccharides, in particular-are the main nutrients contained in mushrooms. And it is precisely mushroom-derived polysaccharides that are increasingly valued for their neuroprotective properties. With additional advantages in terms of low toxicity, biodegradability, stability and low price.
The neuroprotective mechanisms of mushroom polysaccharides have been mainly identified in preventing neuronal apoptosis and oxidative damage, reducingbeta-amyloid protein (Aβ) deposition, inhibiting acetylcholinesterase (to increase the concentration of the neurotransmitter acetylcholine), and regulating neuroinflammation.
Polysaccharides extracted from Dictyophora indusia, Pleurotus ostreatus and Flammulina velutipes have been shown to exhibit neuroprotective effects (Zhang et al., 2016 and 2018). In vitro experiments (Li et al., 2019) with polysaccharides from theAmanita caesarea – a fungus widely cultivated in China–on the hippocampal neuron cell line (HT22), before exposure to L glutamic acid, showed reduction in the decline of cell viability, the rate of apoptosis, the intracellular level of free radicals and changes in the mitochondrial membrane. The polysaccharides of A. caesarea also show an anti-inflammatory effect and improve the function of the cholinergic system in vivo (Hu et al. 2021).
Other evidence has emerged in in vivo experiments conducted with a polysaccharide isolated from the fungus Sparassis crispa, which may alleviate Alzheimer’s symptoms by regulating the gut microbiota and further inhibiting inflammation (Zhang et al., 2023).
Beneficial effects for Alzheimer’s management are also associated with polysaccharides isolated from various fungi(Grifola frondosa, G. lucidum, Armillaria mellea, Cordyceps cicadae, Pleurotus eryngii, Inonotus obliquus, and Tremella fuciformis.
In addition to polysaccharides, oligosaccharides also receive attention in terms of neuroprotection.
3.2 Peptides and proteins
Mushrooms also offer a valuable pool of peptides-a short series of amino acids, the building blocks of our body’s proteins-which show great antioxidant and inflammatory inhibition potential, useful in countering the pathological manifestations of Alzheimer’s.
Growing scientific evidence shows that natural bioactive peptides have great antioxidant and inflammatory inhibition potential, suggesting them as promising candidates for a role in neuroprotection (La Manna et al., 2018).
Cordimin, a peptide isolated from Cordyces sinensis and Cordyceps militaris, can protect against nerve damage in the ischemic brain through its anti-inflammatory and antioxidant actions (Wang et al., 2012).
And again, two peptides derived from selenium-enriched C. militaris can modulate oxidative stress, inflammation, and gut microflora (Wu et al. 2022).
Extensive evidence also concerns ergothioneine. This amino acid shows therapeutic efficacy in various diseases (colorectal cancer, cardiovascular disease), as well as cognitive decline and improvement of clinical symptoms of Alzheimer’s disease. Conversely, a low plasma level of ergothioneine can predict cognitive decline in elderly subjects.
The neuroprotective effect of ergothioneine is associated with its anti-neuroinflammatory, antioxidant, neurogenesis-promoting and neurotrophic factor-inducing abilities (Shah et al., 2015, Ishimoto et al., 2022, Nakamichi et al., 2022).
Some mushrooms are particularly rich in ergothioneine. One of the studies considered (Gioia Dubost et al., 2007) shows significantly higher antioxidant potential in A. bisporus (meadow mushroom) than in the other mushrooms tested.
3.3 Phenolic compounds
Phenolic compounds, whose presence is common in fungi, in turn have garnered much attention from researchers. These bioactive compounds can be classified into several classes, including flavonoids, phenolic acids, tannins, coumarins, etc.
Numerous studies show that phenolic compounds in mushrooms have a wide range of health benefits, including anticancer, antioxidant, and antimicrobial properties. However, the protective ability of mushroom phenolics against neurological diseases deserves further investigation.
3.4 Terpenes
Terpenes are organic compounds that contribute to the smell, taste and fragrance of vegetables and mushrooms. Some terpenes isolated from fungi appear to be useful in improving the pathology of neurodegenerative diseases.
Prolonged application of G. lucidum tritepenoids improved the decline of physiological brain function in aged mice (Zeng et al. 2021). Another study (Jia et al., 2021) demonstrated in vitro the antineuroinflammatory capacity of ganoderic acid A, the lanostane-type triterpenoid from the fungus G. lucidum, known in China for its medicinal properties.
H. erinaceus mycelium enriched with erinacins has shown protective ability against Parkinson’s disease, Alzheimer’s disease, spinocerebellar ataxia type 3, age-related cognitive decline, etc.
In one study (Li et al., 2020), it was found that Alzheimer’s patients treated with three capsules of H. erinaceus mycelia (containing 5 mg/g of erinacin A) showed significant neurocognitive improvement, compared with the control group.
3.5 Vitamins
Vitamin deficiency is associated with diseases of the nervous system, including Parkinson’s and Alzheimer’s. One study (Mavraki et al., 2020) found over-65 Alzheimer’s patients had significantly lower serum vitamin D levels than the control group. Other research also shows involvement of vitamins K2, A and E.
Mushrooms are generally considered natural sources of various vitamins, especially vitamin D2. This makes them potentially useful in controlling Alzheimer’s disease. But the literature on the subject is still scarce.
In one study (Bennet et al., 2013) the function of vitamin D2-enriched champignon mushrooms(Agaricus bisporus) on memory improvement in mice with Alzheimer’s disease was demonstrated.
3.6 Nucleosides
Mushroom nucleosides and their analogs are themselves considered promising as therapeutic drugs for the treatment of Alzheimer’s disease.
Various nucleosides, such as adenosine, cytidine and uridine, have also been isolated because of their role in regulating various physiological processes (brain function, immunity, repair of gastrointestinal injuries, etc.).
In terms of neuroprotection, the typical representative of these is cordicepin, initially extracted from a fungus of the genus Cordyceps, a parasitic fungus that lives at the expense of caterpillars, now also cultivated. Scientific evidence (Yao et al., 2019) shows that chordicepin can regulate synaptic plasticity and overexcitation of the CA1 region (hippocampus), has anti-neuroinflammatory, antioxidant, and anti-apoptosis effects, and can regulate mitochondrial dysfunction, thereby delaying pathological changes caused by neurological diseases.
Adenosine, another key purine nucleoside, from C. cicadae shows protective properties of the neurological system (Olatunji et al. 2016).
3.7 Alkaloids
Alkaloids are nitrogen-containing compounds consisting of various subclasses. In addition to being widely found in plants, alkaloids are important metabolites in fungi (especially psilocybin). With improved separation technology for natural products, various alkaloids have been purified from fungi, and some of them-such as corallocins and infractopicrin-have been shown to have the potential to alleviate neurodegenerative diseases (Shi et al., 2014).
The efficacy of the mushroom Hericium coralloides-which is deeply rooted in Chinese medicine-in promoting the biosynthesis of NGF, nerve growth factor, has been demonstrated both in vitro and in vivo (Wittstein et al., 2016).
3.8 Sterols
Compared with other components, studies on the neuroprotective effects of mushroom sterols are still few.
Although several in vitro experiments have confirmed the neuroprotective effects of mushroom sterols, further work is needed to evaluate their possibility and mechanisms in the treatment of Alzheimer’s disease in vivo, as well as the identification of new mushroom sterols.
Marta Strinati
Notes
(1) Tong Z, Chu G, Wan C, Wang Q, Yang J, Meng Z, Du L, Yang J, Ma H. Multiple Metabolites Derived from Mushrooms and Their Beneficial Effect on Alzheimer’s Diseases. Nutrients. 2023; 15(12):2758. https://doi.org/10.3390/nu15122758
(2) Dario Dongo. Italy, a people of the elderly and disabled. ISTAT Report 2022. Égalité. 17.4.23
Professional journalist since January 1995, he has worked for newspapers (Il Messaggero, Paese Sera, La Stampa) and periodicals (NumeroUno, Il Salvagente). She is the author of journalistic surveys on food, she has published the book "Reading labels to know what we eat".