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Red mold fermented products and Alzheimer's disease: a review

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Abstract

Alzheimer's disease is seen mainly in individuals over the age of 65, and the morbidity rate increases with age. Regarding the health function of Monascus-fermented red mold rice (RMR), besides hypolipidemic and hypotensive effects, other health functions of RMR such as anti-oxidation, cancer prevention, anti-fatigue, and anti-obesity have also been reported. Many published studies have shown the efficacy of RMR in the prevention of Alzheimer's disease. The current article discusses and provides evidence to support the beneficial potential of RMR in the prevention of Alzheimer's disease by discussing the pathogenic factors of Alzheimer's disease and the secondary metabolites of Monascus.

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References

  • Akihisa T, Mafune S, Ukiya M, Kimura Y, Yasukawa K, Suzuki T, Tokuda H, Tanabe N, Fukuoka T (2004) (+)- and (−)-syn-2-isobutyl-4-methylazetidine −2,4-dicarboxylic acids from the extract of Monascus pilosus-fermented rice (red-mold rice). J Nat Prod 67:479–480

    Article  CAS  Google Scholar 

  • Akihisa T, Tokuda H, Yasukawa K, Ukiya M, Kiyota A, Sakamoto N, Suzuki T, Tanabe N, Nishino H (2005) Azaphilones, furanoisophthalides, and amino acids from the extracts of Monascus pilosus-fermented rice (red-mold rice) and their chemopreventive effects. J Agric Food Chem 53:562–565

    Article  CAS  Google Scholar 

  • Andrews-Zwilling Y, Bien-Ly N, Xu Q, Li G, Bernardo A, Yoon SY, Zwilling D, Yan TX, Chen L, Huang Y (2010) Apolipoprotein E4 causes age- and tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice. J Neurosci 30:13707–13717

    Article  CAS  Google Scholar 

  • Aniya Y, Ohtani II, Higa T, Miyagi C, Gibo H, Shimabukuro M, Nakanishi H, Taira J (2000) Dimerumic acid as an antioxidant of the mold, Monascus anka. Free Radic Biol Med 28:999–1004

    Article  CAS  Google Scholar 

  • Araki W, Kitaguchi N, Tokushima Y, Ishii Y, Aratake K, Shimohama H, Nakamura S, Kimura J (1991) Trophic effect of beta-amyloid precursor protein on cerebral cortical neurons in culture. Biochem Biophys Res Commun 181:265–271

    Article  CAS  Google Scholar 

  • Buxbaum JD, Thinakaran G, Koliatsos V, O'Callahan J, Slunt HH, Price DL, Sisodia SS (1998) Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path. J Neurosci 18:9629–9637

    CAS  Google Scholar 

  • Checler F (1995) Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease. J Neurochem 65:1431–1444

    Article  CAS  Google Scholar 

  • Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE (2000) Inflammatory mechanisms in Alzheimer's disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists. J Neurosci 20:558–567

    CAS  Google Scholar 

  • Cordle A, Koenigsknecht-Talboo J, Wilkinson B, Limpert A, Landreth G (2005) Mechanisms of statin-mediated inhibition of small G-protein function. J Biol Chem 280:34202–34209

    Article  CAS  Google Scholar 

  • Cordle A, Landreth G (2005) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses. J Neurosci 25:299–307

    Article  CAS  Google Scholar 

  • Crisby M, Carlson LA, Winblad B (2002) Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis Assoc Disord 16:131–136

    Article  CAS  Google Scholar 

  • Endo A (1979) Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. The Journal of Antibiot (Tokyo) 32:852–854

    CAS  Google Scholar 

  • Esposito G, De Filippis D, Maiuri MC, De Stefano D, Carnuccio R, Iuvone T (2006) Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett 399:91–95

    Article  CAS  Google Scholar 

  • Fassbender K, Stroick M, Bertsch T, Ragoschke A, Kuehl S, Walter S, Walter J, Brechtel K, Muehlhauser F, Von Bergmann K, Lutjohann D (2002) Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide. Neurology 59:1257–1258

    CAS  Google Scholar 

  • Frears ER, Stephens DJ, Walters CE, Davies H, Austen BM (1999) The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport 10:1699–1705

    Article  CAS  Google Scholar 

  • Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 63:1402–1408

    Article  Google Scholar 

  • Ghribi O, Larsen B, Schrag M, Herman MM (2006) High cholesterol content in neurons increases BACE, beta-amyloid, and phosphorylated tau levels in rabbit hippocampus. Exp Neurol 200:460–467

    Article  CAS  Google Scholar 

  • Giacobini E, Mori F, Lai CC (1996) The effect of cholinesterase inhibitors on the secretion of APPS from rat brain cortex. Ann N Y Acad Sci 777:393–398

    Article  CAS  Google Scholar 

  • Hashimoto M, Hossain S, Agdul H, Shido O (2005) Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid beta-infused rats relates to the decreases of amyloid beta and cholesterol levels in detergent-insoluble membrane fractions. Biochim Biophys Acta 1738:91–98

    CAS  Google Scholar 

  • Hauss-Wegrzyniak B, Dobrzanski P, Stoehr JD, Wenk GL (1998) Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer's disease. Brain Res 780:294–303

    Article  CAS  Google Scholar 

  • Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA (2000) Statins and the risk of dementia. Lancet 356:1627–1631

    Article  CAS  Google Scholar 

  • Juzlova PM, Martinkova L, Kren V (1996) Secondary metabolites of the fungus Monascus: a review. J Ind Microbiol 16:163–170

    Article  CAS  Google Scholar 

  • Kirsch C, Eckert GP, Mueller WE (2003) Statin effects on cholesterol micro-domains in brain plasma membranes. Biochem Pharmacol 65:843–856

    Article  CAS  Google Scholar 

  • Kuo YM, Emmerling MR, Bisgaier CL, Essenburg AD, Lampert HC, Drumm D, Roher AE (1998) Elevated low-density lipoprotein in Alzheimer's disease correlates with brain abeta 1–42 levels. Biochem Biophys Res Commun 252:711–715

    Article  CAS  Google Scholar 

  • Lee CL, Kuo TF, Wang JJ, Pan TM (2007) Red mold rice ameliorates impairment of memory and learning ability in intracerebroventricular amyloid beta-infused rat by repressing amyloid beta accumulation. J Neurosci Res 85:3171–3182

    Article  CAS  Google Scholar 

  • Lee CL, Kuo TF, Wu CL, Wang JJ, Pan TM (2010) Red mold rice promotes neuroprotective sAPPalpha secretion instead of Alzheimer's risk factors and amyloid beta expression in hyperlipidemic Abeta40-infused rats. J Agric Food Chem 58:2230–2238

    Article  CAS  Google Scholar 

  • Lee CL, Tsai TY, Wang JJ, Pan TM (2006a) In vivo hypolipidemic effects and safety of low dosage Monascus powder in a hamster model of hyperlipidemia. Appl Microbiol Biotechnol 70:533–540

    Article  CAS  Google Scholar 

  • Lee CL, Wang JJ, Pan TM (2008) Red mold rice extract represses amyloid beta peptide-induced neurotoxicity via potent synergism of anti-inflammatory and antioxidative effect. Appl Microbiol Biotechnol 79:829–841

    Article  CAS  Google Scholar 

  • Lee CL, Wang JJ, Kuo SL, Pan TM (2006b) Monascus fermentation of dioscorea for increasing the production of cholesterol-lowering agent-monacolin K and antiinflammation agent-monascin. Appl Microbiol Biotechnol 72:1254–1262

    Article  CAS  Google Scholar 

  • Li L, Cao D, Kim H, Lester R, Fukuchi K (2006) Simvastatin enhances learning and memory independent of amyloid load in mice. Ann Neurol 60:729–739

    Article  CAS  Google Scholar 

  • Liao JK (2002) Isoprenoids as mediators of the biological effects of statins. J Clin Invest 110:285–288

    CAS  Google Scholar 

  • Liao JK, Laufs U (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45:89–118

    Article  CAS  Google Scholar 

  • Ma J, Li Y, Ye Q, Li J, Hua Y, Ju D, Zhang D, Cooper R, Chang M (2000) Constituents of red yeast rice, a traditional Chinese food and medicine. J Agric Food Chem 48:5220–5225

    Article  CAS  Google Scholar 

  • Mackenzie IR, Munoz DG (1998) Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 50:986–990

    CAS  Google Scholar 

  • Morimoto T, Ohsawa I, Takamura C, Ishiguro M, Kohsaka S (1998) Involvement of amyloid precursor protein in functional synapse formation in cultured hippocampal neurons. J Neurosci Res 51:185–195

    Article  CAS  Google Scholar 

  • Naidu A, Xu Q, Catalano R, Cordell B (2002) Secretion of apolipoprotein E by brain glia requires protein prenylation and is suppressed by statins. Brain Res 958:100–111

    Article  CAS  Google Scholar 

  • Perez‐Severiano F, Rodriguez‐Perez M, Pedraza‐Chaverri J, Maldonado PD, Medina‐Campos ON, Ortiz‐Plata A, Sanchez‐Garcia A, Villeda‐Hernandez J, Galvan‐Arzate S, Aguilera P, Santamaria A (2004) S‐Allylcysteine, a garlic‐derived antioxidant, ameliorates quinolinic acid‐induced neurotoxicity and oxidative damage in rats. Neurochem Int 45:1175–1183

    Google Scholar 

  • Poirier J (2003) Apolipoprotein E and cholesterol metabolism in the pathogenesis and treatment of Alzheimer's disease. Trends Mol Med 9:94–101

    Article  CAS  Google Scholar 

  • Pollen DA, Baker S, Hinerfeld D, Swearer J, Evans BA, Evans JE, Caselli R, Rogaeva E, St George-Hyslop P, Moonis M (2010) Prevention of Alzheimer's disease in high risk groups: statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein E epsilon 4. Alzheimers Res Ther 2:31

    Article  Google Scholar 

  • Rockwood K, Kirkland S, Hogan DB, MacKnight C, Merry H, Verreault R, Wolfson C, McDowell I (2002) Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 59:223–227

    Article  Google Scholar 

  • Roher AE, Kuo YM (1999) Isolation of amyloid deposits from brain. Methods Enzymol 309:58–67

    Article  CAS  Google Scholar 

  • Sastre M, Klockgether T, Heneka MT (2006) Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms. Int J Dev Neurosci 24:167–176

    Article  CAS  Google Scholar 

  • Schubert D, Behl C (1993) The expression of amyloid beta protein precursor protects nerve cells from beta-amyloid and glutamate toxicity and alters their interaction with the extracellular matrix. Brain Res 629:275–282

    Article  CAS  Google Scholar 

  • Schubert D, Behl C, Lesley R, Brack A, Dargusch R, Sagara Y, Kimura H (1995) Amyloid peptides are toxic via a common oxidative mechanism. Proc Natl Acad Sci USA 92:1989–1993

    Article  CAS  Google Scholar 

  • Small DH, Nurcombe V, Reed G, Clarris H, Moir R, Beyreuther K, Masters CL (1994) A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J Neurosci 14:2117–2127

    CAS  Google Scholar 

  • Stewart R (1998) Cardiovascular factors in Alzheimer's disease. J Neurol Neurosurg Psychiatry 65:143–147

    Article  CAS  Google Scholar 

  • Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90:1977–1981

    Article  CAS  Google Scholar 

  • Su YC, Wang JJ, Lin TT, Pan TM (2003) Production of the secondary metabolites gamma-amino butyric acid and monacolin K by Monascus. J Ind Microbiol Biotechnol 30:41–46

    CAS  Google Scholar 

  • Tang F, Nag S, Shiu SY, Pang SF (2002) The effects of melatonin and Ginkgo biloba extract on memory loss and choline acetyltransferase activities in the brain of rats infused intracerebroventricularly with beta-amyloid 1–40. Life Sci 71:2625–2631

    Article  CAS  Google Scholar 

  • Townsend KP, Pratico D (2005) Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J 19:1592–1601

    Article  CAS  Google Scholar 

  • Wang R, Zhang HY, Tang XC (2001) Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1–40) in rat. Eur J Pharmacol 421:149–156

    Article  CAS  Google Scholar 

  • Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G (2000) Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 57:1439–1443

    Article  CAS  Google Scholar 

  • Wong HC, Bau YS (1977) Pigmentation and antibacterial activity of fast neutron- and x-ray-induced strains of Monascus purpureus Went. Plant Physiol 60:578–581

    Article  CAS  Google Scholar 

  • Yamada K, Ren X, Nabeshima T (1999) Perspectives of pharmacotherapy in Alzheimer’s disease. Jpn J Pharmacol 80:9–14

    Google Scholar 

  • Yamaguchi Y, Miyashita H, Tsunekawa H, Mouri A, Kim HC, Saito K, Matsuno T, Kawashima S, Nabeshima T (2006) Effects of a novel cognitive enhancer, spiro[imidazo‐[1,2‐a]pyridine‐3,2‐indan]‐2(3H)‐one (ZSET1446), on learning impairments induced by amyloid‐beta1‐40 in the rat. J Pharmacol Exp Ther 317:1079–1087

    Google Scholar 

  • Zhao B (2005) Natural antioxidants for neurodegenerative diseases. Mol Neurobiol 31:283–293

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Life Science, National Taitung University, Taitung, Taiwan, ROC

    Chun-Lin Lee

  2. Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan, ROC

    Tzu-Ming Pan

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  1. Chun-Lin Lee
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Correspondence to Tzu-Ming Pan.

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Lee, CL., Pan, TM. Red mold fermented products and Alzheimer's disease: a review. Appl Microbiol Biotechnol 91, 461–469 (2011). https://doi.org/10.1007/s00253-011-3413-1

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