Role of Mushrooms in Neurodegenerative Diseases

  • Wooseok Lee
  • Ayaka Fujihashi
  • Manoj Govindarajulu
  • Sindhu Ramesh
  • Jack Deruiter
  • Mohammed Majrashi
  • Mohammed Almaghrabi
  • Rishi M. Nadar
  • Timothy Moore
  • Dinesh Chandra AgrawalEmail author
  • Muralikrishnan DhanasekaranEmail author


Mushrooms have extensively been used not only as a dietary intake but also for the treatment of various central nervous system (CNS) and peripheral nervous system (PNS) disorders. At its early stages, accumulated evidence has suggested that culinary-medicinal mushrooms may play a significant role in the prevention of many age-associated neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Therefore, further research and efforts have been devoted to a search for more mushroom species that may improve memory and cognitive functions and, in addition, prevent the progression of dementia and neurodegeneration. Such mushrooms include Hericium erinaceus, Ganoderma lucidum, Lignosus rhinocerotis, Pleurotus giganteus, Sarcodon scabrosus, Antrodia camphorata, Paxillus panuoides, Mycoleptodonoides aitchisonii, and several other species. This review focuses on the various abovementioned neuroprotective, culinary-medicinal mushrooms and the bioactive secondary metabolites isolated from them. The mushrooms’ extracts from basidiocarps/mycelia or isolated compounds have been known to decrease neurotoxicity through various neuroprotective molecular mechanisms such as anti-acetylcholinesterase activity, neurite outgrowth stimulation (neuritogenic), and nerve growth factor (NGF) synthesis (neurotrophic), enhancing mitochondrial functions and reducing endoplasmic reticulum (ER) stress, in addition to antioxidant and anti-inflammatory effects. Therefore, mushrooms can be considered as useful therapeutic agents in the prevention, management, and/or treatment of neurodegenerative diseases.


Antioxidant Culinary mushroom Neuritogenic Neurodegeneration Neuroprotection Neurotoxicity Neurotrophic 





Alzheimer’s disease


ɑ-Ketoglutarate dehydrogenase


Amyotrophic lateral sclerosis




Blood-brain barrier




Central nervous system


Deoxyribonucleic acid


Ethanol extract of Ganoderma lucidum


Endoplasmic reticulum


Huntington’s disease


Heme oxygenase-1


Heat Shock Protein 70




Interleukin 1β






Lipoxin A4


Nuclear factor-kappa B


Nerve growth factor


Nitric oxide


Parkinson’s disease


Pyruvate dehydrogenase


Prostaglandin E2


Peripheral nervous system


Reactive oxygen species


Succinate dehydrogenase


Toll-like receptor


Tumor necrosis factor-alpha




  1. Ajith TA, Sudheesh NP, Roshny D, Abishek G, Janardhanan KK (2009) Effect of Ganoderma lucidum on the activities of mitochondrial dehydrogenases and complex I and II of electron transport chain in the brain of aged rats. Exp Gerontol 44:219–223. CrossRefPubMedGoogle Scholar
  2. Ao ZH, Xu ZH, Lu ZM, Xu HY, Zhang XM, Dou WF (2009) Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases. J Ethnopharmacol 121:194–212. CrossRefPubMedGoogle Scholar
  3. Badham ER (1984) Ethnobotany of psilocybin mushrooms, especially Psilocybe cubensis. J Ethnopharmacol 10:249–254. CrossRefPubMedGoogle Scholar
  4. Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214. CrossRefPubMedGoogle Scholar
  5. Baskaran A, Chua KH, Sabaratnam V, Ravishankar Ram M, Kuppusamy UR (2017) Pleurotus giganteus (Berk. Karun & Hyde), the giant oyster mushroom inhibits NO production in LPS/H2O2 stimulated RAW 264.7 cells via STAT 3 and COX-2 pathways. BMC Complement Altern Med 17:40. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Benjamin C (1979) Persistent psychiatric symptoms after eating psilocybin mushrooms. Br Med J 1:1319–1320CrossRefGoogle Scholar
  7. Chia Wei P (2015) Neurite outgrowth stimulatory activity of an edible mushroom Pleurotus giganteus in differentiating neuroblastoma-2a cells. Thesis, University of Malaya, Kuala LumpurGoogle Scholar
  8. Chien SC, Chen ML, Kuo HT, Tsai YC, Lin BF, Kuo YH (2008) Anti-inflammatory activities of new succinic and maleic derivatives from the fruiting body of Antrodia camphorata. J Agric Food Chem 56:7017–7022. CrossRefPubMedGoogle Scholar
  9. Choi D, Lee JH, Kim YS, Na M-S, Choi OY, Lee HD, Lee MK, Cha WS (2011) A study of mycelial growth and exopolysaccharide production from a submerged culture of Mycoleptodonoides aitchisonii in an air-lift bioreactor. Korean J Chem Eng 28:1427–1432. CrossRefGoogle Scholar
  10. Choi JH, Suzuki T, Okumura H, Noguchi K, Kondo M, Nagai K, Hirai H, Kawagishi H (2014) Endoplasmic reticulum stress suppressive compounds from the edible mushroom Mycoleptodonoides aitchisonii. J Nat Prod 77:1729–1733. CrossRefGoogle Scholar
  11. Choi MH, Wu Y, Oh DS, Kim SK, Shin HJ (2016) Antioxidant and antidiabetic activities of mycelial and fruit-body extracts from Mycoleptodonoides aitchisonii. Biotechnol Bioprocess Eng 21:355–363. CrossRefGoogle Scholar
  12. Eik LF, Naidu M, David P, Wong KH, Tan YS, Sabaratnam V (2012) Lignosus rhinocerus (Cooke) Ryvarden: a medicinal mushroom that stimulates neurite outgrowth in PC-12 cells. Evid Based Complement Alternat Med 2012:320308. CrossRefGoogle Scholar
  13. Geethangili M, Tzeng YM (2011) Review of pharmacological effects of Antrodia camphorata and its bioactive compounds. Evid Based Complement Alternat Med 2011:212641. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Geissler T, Brandt W, Porzel A, Schlenzig D, Kehlen A, Wessjohann L, Arnold N (2010) Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus. Bioorg Med Chem 18:2173–2177. CrossRefGoogle Scholar
  15. Giridharan VV, Thandavarayan RA, Konishi T (2011) Amelioration of scopolamine induced cognitive dysfunction and oxidative stress by Inonotus obliquus– a medicinal mushroom. Food Funct 2:320. CrossRefPubMedGoogle Scholar
  16. Hsiao G, Shen MY, Lin KH, Lan MH, Wu LY, Chou DS, Lin CH, Su CH, Sheu JR (2003) Antioxidative and hepatoprotective effects of Antrodia camphorata extract. J Agric Food Chem. CrossRefGoogle Scholar
  17. Huang NK, Cheng JJ, Lai WL, Lu MK (2005) Antrodia camphorata prevents rat pheochromocytoma cells from serum deprivation-induced apoptosis. FEMS Microbiol Lett 244:213–219. CrossRefPubMedGoogle Scholar
  18. Jo WS, Hossain MA, Park SC (2014) Toxicological profiles of poisonous, edible, and medicinal mushrooms. Mycobiology 42:215–220. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Journal O, Xu T, Beelman RB (2015) The bioactive compounds in medicinal mushrooms have potential protective effects against neurodegenerative diseases. Adv Food Technol Nutr Sci 1:62–65. CrossRefGoogle Scholar
  20. Kawagishi H, Shimada A, Shirai R, Okamoto K, Ojima F, Sakamoto H, Ishiguro Y, Furukawa S (1994) Erinacines A, B and C, strong stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceus. Tetrahedron Lett 35:1569–1572. CrossRefGoogle Scholar
  21. Khatun K, Mahtab H, Khanam PA, Sayeed MA, Khan KA (2007) Oyster mushroom reduced blood glucose and cholesterol in diabetic subjects. Mymensingh Med J 16:94–99CrossRefGoogle Scholar
  22. Kim EK, Lee SJ, Hwang JW, Kim CG, Choi DK, Lim BO, Kang H, Moon SH, Jeon BT, Park PJ (2011) In Vitro investigation on antioxidative effect of Inonotus obliquus extracts against oxidative stress on PC12 cells. J Korean Soc Appl Biol Chem 54:112–117. CrossRefGoogle Scholar
  23. Lee IK, Yun BS, Han G, Cho DH, Kim YH, Yoo ID (2002) Dictyoquinazols A, B, and C, new neuroprotective compounds from the mushroom Dictyophora indusiata. J Nat Prod 65:1769–1772. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Lee IK, Yun BS, Kim JP, Ryoo IJ, Kim YH, Yoo ID (2003) Neuroprotective activity of p-terphenyl leucomentins from the mushroom Paxillus panuoides. Biosci Biotechnol Biochem 67:1813–1816. CrossRefPubMedGoogle Scholar
  25. Lee I, Ahn B, Choi J, Hattori M, Min B, Bae K (2011) Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum. Bioorg Med Chem Lett 21:6603–6607. CrossRefGoogle Scholar
  26. Lima ADL, Costa Fortes R, Carvalho Garbi Novaes MR, Percário S (2012) Poisonous mushrooms: a review of the most common intoxications. Nutr Hosp 27:402–408. CrossRefGoogle Scholar
  27. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795. CrossRefPubMedPubMedCentralGoogle Scholar
  28. Lin JM, Lin CC, Chen MF, Ujiie T, Takada A (1995) Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum. J Ethnopharmacol 47:33–41CrossRefGoogle Scholar
  29. Ling Sing Seow S, Naidu M, David P, Wong KH, Sabaratnam V (2013) Potentiation of neuritogenic activity of medicinal mushrooms in rat pheochromocytoma cells. BMC Complement Altern Med 13:157. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Mcdonald A (1980) Mushrooms and madness: hallucinogenic mushrooms and some psychopharmacological implications. Can J Psychiatr 25:586–594. CrossRefGoogle Scholar
  31. McGeer PL, McGeer EG (1995) The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 21:195–218CrossRefGoogle Scholar
  32. Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N (2008) Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biol Pharm Bull 31:1727–1732CrossRefGoogle Scholar
  33. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T (2009) Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phyther Res 23:367–372. CrossRefGoogle Scholar
  34. Murphy MP, LeVine H (2010) Alzheimer’s disease and the amyloid-β peptide. J Alzheimers Dis 19:311–323. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Nallathamby N, Phan CW, Seow SLS, Baskaran A, Lakshmanan H, Abd Malek SN, Sabaratnam V (2018) A status review of the bioactive activities of tiger milk mushroom Lignosus rhinocerotis (Cooke) Ryvarden. Front Pharmacol 8:998. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Nishina A, Kimura H, Sekiguchi A, Fukumoto R, Nakajima S, Furukawa S (2006) Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via activation of MAPK. J Lipid Res 47:1434–1443. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Ohta T, Kita T, Kobayashi N, Obara Y, Nakahata N, Ohizumi Y, Takaya Y, Oshima Y (1998) Scabronine A, a novel diterpenoid having potent inductive activity of the nerve growth factor synthesis, isolated from the mushroom, Sarcodon scabrosus. Tetrahedron Lett 39:6229–6232. CrossRefGoogle Scholar
  38. Okuyama S, Lam NV, Hatakeyama T, Terashima T, Yamagata K, Yokogoshi H (2004) Mycoleptodonoides aitchisonii affects brain nerve growth factor concentration in newborn rats. Nutr Neurosci 7:341–349. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Park KJ, Lee SY, Kim HS, Yamazaki M, Chiba K, Ha H-C (2007) The neuroprotective and neurotrophic effects of Tremella fuciformis in PC12h cells. Mycobiology 35:11–15. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Park HJ, Shim HS, Ahn YH, Kim KS, Park KJ, Choi WK, Ha HC, Il KJ, Kim TS, Yeo IH, Kim JS, Shim I (2012) Tremella fuciformis enhances the neurite outgrowth of PC12 cells and restores trimethyltin-induced impairment of memory in rats via activation of CREB transcription and cholinergic systems. Behav Brain Res 229:82–90. CrossRefPubMedGoogle Scholar
  41. Phan CW, David P, Naidu M, Wong KH, Sabaratnam V (2015) Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Crit Rev Biotechnol 35:355–368. CrossRefPubMedPubMedCentralGoogle Scholar
  42. Przedborski S, Vila M, Jackson Lewis V (2003) Neurodegeneration: what is it and where are we? J Clin Invest 111:3–10. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Qi J, Ojika M, Sakagami Y (2000) Termitomycesphins A–D, novel neuritogenic cerebrosides from the edible chinese mushroom Termitomyces albuminosus. Tetrahedron 56:5835–5841. CrossRefGoogle Scholar
  44. Qu Y, Sun K, Gao L, Sakagami Y, Kawagishi H, Ojika M, Qi J (2012) Termitomycesphins G and H, additional cerebrosides from the edible Chinese mushroom Termitomyces albuminosus. Biosci Biotechnol Biochem 76:791–793. CrossRefGoogle Scholar
  45. Quang DN, Hashimoto T, Nukada M, Yamamoto I, Tanaka M, Asakawa Y (2003) Curtisians E-H: four p-terphenyl derivatives from the inedible mushroom Paxillus curtisii. Phytochemistry 64:649–654CrossRefGoogle Scholar
  46. Sabaratnam V, Kah-Hui W, Naidu M, David PR (2013) Neuronal health – can culinary and medicinal mushrooms help? J Tradit Complement Med 3:62–68. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Seow SLS, Eik LF, Naidu M, David P, Wong KH, Sabaratnam V (2015) Lignosus rhinocerotis (Cooke) Ryvarden mimics the neuritogenic activity of nerve growth factor via MEK/ERK1/2 signaling pathway in PC-12 cells. Sci Rep 5:16349. CrossRefPubMedPubMedCentralGoogle Scholar
  48. Shi XW, Liu L, Gao JM, Zhang AL (2011) Cyathane diterpenes from Chinese mushroom Sarcodon scabrosus and their neurite outgrowth-promoting activity. Eur J Med Chem 46:3112–3117. CrossRefPubMedGoogle Scholar
  49. Shibata H, Irie A, Morita Y (1998) New antibacterial diterpenoids from the Sarcodon scabrosus fungus. Biosci Biotechnol Biochem 62:2450–2452. CrossRefPubMedGoogle Scholar
  50. Skovronsky DM, Lee VMY, Trojanowski JQ (2006) Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol Mech Dis 1:151–170. CrossRefGoogle Scholar
  51. Soytong K, Asue T (2012) Study on physiological and cultural requirements of Pleurotus giganteus. Int J Agric Technol 10:923–930Google Scholar
  52. Sticht G, Käferstein H (2000) Detection of psilocin in body fluids. Forensic Sci Int 113:403–407. CrossRefPubMedGoogle Scholar
  53. Teichert A, Schmidt J, Porzel A, Arnold N, Wessjohann L (2007) Brunneins A–C, β-carboline alkaloids from Cortinarius brunneus. J Nat Prod 70:1529–1531. CrossRefPubMedGoogle Scholar
  54. Trovato Salinaro A, Pennisi M, Di Paola R, Scuto M, Crupi R, Cambria MT, Ontario ML, Tomasello M, Uva M, Maiolino L, Calabrese EJ, Cuzzocrea S, Calabrese V (2018) Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: modulation by nutritional mushrooms. Immun Ageing 15:8. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Trovato A, Siracusa R, Di Paola R, Scuto M, Fronte V, Koverech G, Luca M, Serra A, Toscano MA, Petralia A, Cuzzocrea S, Calabrese V (2016) Redox modulation of cellular stress response and lipoxin A4 expression by Coriolus versicolor in rat brain: relevance to Alzheimer’s disease pathogenesis. Neurotoxicology 53:350–358. CrossRefPubMedGoogle Scholar
  56. Ueda K, Tsujimori M, Kodani S, Chiba A, Kubo M, Masuno K, Sekiya A, Nagai K, Kawagishi H (2008) An endoplasmic reticulum (ER) stress-suppressive compound and its analogues from the mushroom Hericium erinaceum. Bioorg Med Chem 16:9467–9470. CrossRefPubMedGoogle Scholar
  57. Wachtel Galor S, Yuen J, Buswell JA, Benzie IFF (2011) Ganoderma lucidum (Lingzhi or Reishi): a medicinal mushroom. Oxid Stress Dis 28:175–200Google Scholar
  58. Wang Z, Luo D, Liang Z (2004) Structure of polysaccharides from the fruiting body of Hericium erinaceus Pers. Carbohydr Polym 57:241–247. CrossRefGoogle Scholar
  59. Wang LC, Wang SE, Wang JJ, Tsai TY, Lin CH, Pan TM, Lee CL (2012) In vitro and in vivo comparisons of the effects of the fruiting body and mycelium of Antrodia camphorata against amyloid β-protein-induced neurotoxicity and memory impairment. Appl Microbiol Biotechnol 94:1505–1519. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Wasser S (2002) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60:258–274. CrossRefGoogle Scholar
  61. Waters SP, Tian Y, Li YM, Danishefsky SJ (2005) Total synthesis of (−)-scabronine G, an inducer of neurotrophic factor production. J Am Chem Soc 127:13514–13515. CrossRefPubMedGoogle Scholar
  62. Wender PA, Bi FC, Brodney MA, Gosselin F (2001) Asymmetric synthesis of the tricyclic core of NGF-inducing cyathane diterpenes via a transition-metal-catalyzed [5 + 2] cycloaddition. Org Lett 3:2105–2108CrossRefGoogle Scholar
  63. Yap YH, Tan N, Fung S, Aziz AA, Tan C, Ng S (2013) Nutrient composition, antioxidant properties, and anti-proliferative activity of Lignosus rhinocerus Cooke sclerotium. J Sci Food Agric 93:2945–2952. CrossRefPubMedPubMedCentralGoogle Scholar
  64. Yoon HM, Jang KJ, Han MS, Jeong JW, Kim GY, Lee JH, Choi YH (2013) Ganoderma lucidum ethanol extract inhibits the inflammatory response by suppressing the NF-κB and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglial cells. Exp Ther Med 5:957–963. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Yun BS, Lee IK, Kim JP, Yoo ID (2000) Leucomentin-5 and -6, two new leucomentin derivatives from the mushroom Paxillus panuoides. J Antibiot (Tokyo) 53:711–713CrossRefGoogle Scholar
  66. Zhang R, Xu S, Cai Y, Zhou M, Zuo X, Chan P (2011) Ganoderma lucidum protects dopaminergic neuron degeneration through inhibition of microglial activation. Evid Based Complement Alternat Med 2011:156810. CrossRefPubMedPubMedCentralGoogle Scholar
  67. Zhou Y, Qu Z, Zeng Y, Lin Y, Li Y, Chung P, Wong R, Hägg U (2012) Neuroprotective effect of preadministration with Ganoderma lucidum spore on rat hippocampus. Exp Toxicol Pathol 64:673–680. CrossRefGoogle Scholar
  68. Zinkand WC, Moore WC, Thompson C, Salama AI, Patel J (1992) Ibotenic acid mediates neurotoxicity and phosphoinositide hydrolysis by independent receptor mechanisms. Mol Chem Neuropathol 16:1–10. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Wooseok Lee
    • 1
  • Ayaka Fujihashi
    • 1
  • Manoj Govindarajulu
    • 1
  • Sindhu Ramesh
    • 1
  • Jack Deruiter
    • 1
  • Mohammed Majrashi
    • 1
    • 2
  • Mohammed Almaghrabi
    • 3
  • Rishi M. Nadar
    • 1
  • Timothy Moore
    • 1
  • Dinesh Chandra Agrawal
    • 4
    Email author
  • Muralikrishnan Dhanasekaran
    • 1
    Email author
  1. 1.Department of Drug Discovery and Development, Harrison School of PharmacyAuburn UniversityAuburnUSA
  2. 2.Department of Pharmacology, Faculty of MedicineUniversity of JeddahJeddahKingdom of Saudi Arabia
  3. 3.Department of Pharmaceutical Chemistry, College of PharmacyTaibah UniversityAlmadinah AlmunawwarahKingdom of Saudi Arabia
  4. 4.Department of Applied ChemistryChaoyang University of TechnologyTaichungTaiwan

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