International Journal of Clinical Nutrition & Dietetics Volume 5 (2019), Article ID 5:IJCND-139, 5 pages
Research Article
Neuroprotection Afforded by a Preventive CogniXtra Treatment Against Amyloid Beta Aβ25-35 Peptide-induced Toxicity in Mice

Guillaume Blivet1, Francois J. Roman2*, Johann Meunier2, Laura Ceolin2, Jean-Marie Butterlin3 and Jacques Touchon4,5,6

1Montpellier, France
2Amylgen, Montferrier-sur-Lez, France
3Health Optimisation Devices B.V., Maastricht, Netherlands
4INSERM U1061, Montpellier, France
5Montpellier University, Montpellier, France
6JT Conseils, Montpellier, France
Dr. François J. Roman, Amylgen, 2196, Agropolis 2, boulevard de La Lironde, 34980 Montferrier-sur-Lez, France, Tel: +33 (0)610231475; E-mail:
08 November 2018; 04 February 2019; 06 February 2019
Blivet G, Roman FJ, Meunier J, Ceolin L, Butterlin JM, et al. (2019) Neuroprotection Afforded by a Preventive CogniXtra Treatment Against Amyloid Beta Aβ25-35 Peptide-induced Toxicity in Mice. Int J Clin Nutr Diet 5: 139. doi:
This work was funded by Health Optimisation Devices B.V., Maastricht, Netherlands.


  1. Alzheimer's Association (2016) 2016 Alzheimer's disease facts and figures. Alzheimers Dement 12: 459-509 [CrossRef] [Google Scholar] [PubMed]
  2. Doraiswamy PM (2002) Non-cholinergic strategies for treating and preventing Alzheimer's disease. CNS Drugs 16: 811-824 [CrossRef] [Google Scholar] [PubMed]
  3. Takahata K, Minami A, Kusumoto H, Shimazu S, Yoneda F, et al. (2005) Effects of selegiline alone or with donepezil on memory impairment in rats. Eur J Pharmacol 518: 140-144 [CrossRef] [Google Scholar] [PubMed]
  4. Butterfield DA (1997) beta-Amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimer's disease. Chem Res Toxicol 10: 495-506 [CrossRef] [Google Scholar] [PubMed]
  5. Hu N, Yu JT, Tan L, Wang YL, Sun L, et al. (2013) Nutrition and the risk of Alzheimer's disease. Biomed Res Int 2013: 524820 [CrossRef] [Google Scholar] [PubMed]
  6. Mecocci P, Tinarelli C, Schulz RJ, Polidori MC (2014) Nutraceuticals in cognitive impairment and Alzheimer's disease. Front Pharmacol 5: 147 [CrossRef] [Google Scholar] [PubMed]
  7. Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn AD, et al. (2010) Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial. Dement Geriatr Cogn Disord 29: 467-474 [CrossRef] [Google Scholar] [PubMed]
  8. Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, et al. (2010) Soybeanderived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr 47: 246- 255 [CrossRef] [Google Scholar] [PubMed]
  9. Riggs KM, Spiro A, Tucker K, Rush D (1996) Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 63: 306-314 [CrossRef] [Google Scholar] [PubMed]
  10. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, et al. (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 336: 1216-1222 [CrossRef] [Google Scholar] [PubMed]
  11. Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, et al. (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69: 836-841 [CrossRef] [Google Scholar] [PubMed]
  12. Maurice T, Lockhart BP, Privat A (1996) Amnesia induced in mice by centrally administered beta-amyloid peptides involves cholinergic dysfunction. Brain Res 706: 181-193 [CrossRef] [Google Scholar] [PubMed]
  13. Gruden MA, Davidova TB, Malisauskas M, Sewell RD, Voskresenskaya NI, et al. (2007) Differential neuroimmune markers to the onset of Alzheimer's disease neurodegeneration and dementia: autoantibodies to Abeta (25-35) oligomers, S100b and neurotransmitters. J Neuroimmunol 186: 181-192 [CrossRef] [Google Scholar] [PubMed]
  14. Pike CJ, Burdick D, Walencewicz AJ, Glabe CG, Cotman CW, et al. (1993) Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci 13: 1676-1687 [Google Scholar] [PubMed]
  15. Kubo T, Nishimura S, Kumagae Y, Kaneko I (2002) In vivo conversion of racemized beta-amyloid ([D-Ser 26] A beta 1-40) to truncated and toxic fragments ([D-Ser 26]A beta 25-35/40) and fragment presence in the brains of Alzheimer's patients. J Neurosci Res 70: 474-483 [CrossRef] [Google Scholar] [PubMed]
  16. Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol Chemother 12: 12-15 [Google Scholar] [PubMed]
  17. Meunier J, Villard V, Givalois L, Maurice T (2013) The gamma-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl)amino] ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Abeta1-42 seeding and short-term memory deficits in the Abeta25-35 mouse model of Alzheimer's disease. Eur J Pharmacol 698: 193-199 [CrossRef] [Google Scholar] [PubMed]
  18. Villard V, Espallergues J, Keller E, Vamvakides A, Maurice T, et al. (2011) Antiamnesic and neuroprotective potentials of the mixed muscarinic receptor/ sigma 1 (sigma1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative. J Psychopharmacol 25: 1101-1117 [CrossRef] [Google Scholar] [PubMed]
  19. Hiramatsu M, Inoue K (1999) Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice. Br J Pharmacol 127: 655-660 [CrossRef] [Google Scholar] [PubMed]
  20. Hermes-Lima M, Willmore WG, Storey KB (1995) Quantification of lipid peroxidation in tissue extracts based on Fe(III)xylenol orange complex formation. Free Radic Biol Med 19: 271-280 [CrossRef] [Google Scholar] [PubMed]
  21. Klementiev B, Novikova T, Novitskaya V, Walmod PS, Dmytriyeva O, et al. (2007) A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35. Neuroscience 145: 209-224 [CrossRef] [Google Scholar] [PubMed]
  22. Chavant F, Deguil J, Pain S, Ingrand I, Milin S, et al. (2010) Imipramine, in part through tumor necrosis factor alpha inhibition, prevents cognitive decline and beta-amyloid accumulation in a mouse model of Alzheimer's disease. J Pharmacol Exp Ther 332: 505-514 [CrossRef] [Google Scholar] [PubMed]
  23. Stepanichev MY, Zdobnova IM, Zarubenko, II, Moiseeva YV, Lazareva NA, et al. (2004) Amyloid-beta (25-35)-induced memory impairments correlate with cell loss in rat hippocampus. Physiol Behav 80: 647-655 [CrossRef] [Google Scholar] [PubMed]
  24. Lahmy V, Long R, Morin D, Villard V, Maurice T, et al. (2014) Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25-35 peptide-injected mice, a nontransgenic Alzheimer’s disease model. Front Cell Neurosci 8: 463 [CrossRef] [Google Scholar] [PubMed]
  25. Noh MY, Koh SH, Kim SM, Maurice T, Ku SK, et al. (2013) Neuroprotective effects of donepezil against Abeta42-induced neuronal toxicity are mediated through not only enhancing PP2A activity but also regulating GSK-3beta and nAChRs activity. J Neurochem 127: 562-574 [CrossRef] [Google Scholar] [PubMed]
  26. Stepanichev MY, Zdobnova IM, Zarubenko II, Lazareva NA, Gulyaeva NV, et al. (2006) Studies of the effects of central administration of beta-amyloid peptide (25-35): pathomorphological changes in the Hippocampus and impairment of spatial memory. Neurosci Behav Physiol 36: 101-106 [CrossRef] [Google Scholar] [PubMed]
  27. Stepanichev M, Lazareva N, Tukhbatova G, Salozhin S, Gulyaeva N, et al. (2014) Transient disturbances in contextual fear memory induced by Abeta(25-35) in rats are accompanied by cholinergic dysfunction. Behav Brain Res 259: 152-157 [CrossRef] [Google Scholar] [PubMed]
  28. Zussy C, Brureau A, Delair B, Marchal S, Keller E, et al. (2011) Time-course and regional analyses of the physiopathological changes induced after cerebral injection of an amyloid beta fragment in rats. Am J Pathol 179: 315-334 [CrossRef] [Google Scholar] [PubMed]
  29. Meunier J, Borjini N, Gillis C, Villard V, Maurice T, et al. (2015) Brain toxicity and inflammation induced in vivo in mice by the amyloid-beta forty-two inducer aftin-4, a roscovitine derivative. J Alzheimers Dis 44: 507-524 [CrossRef] [Google Scholar] [PubMed]
  30. Meunier J, Ieni J, Maurice T (2006) The anti-amnesic and neuroprotective effects of donepezil against amyloid beta25-35 peptide-induced toxicity in mice involve an interaction with the sigma1 receptor. Br J Pharmacol 149: 998-1012 [CrossRef] [Google Scholar] [PubMed]
  31. Naert G, Ferre V, Meunier J, Keller E, Malmstrom S, et al. (2015) Leucettine L41, a DYRK1A-preferential DYRKs/CLKs inhibitor, prevents memory impairments and neurotoxicity induced by oligomeric Abeta25-35 peptide administration in mice. Eur Neuropsychopharmacol 25: 2170-2182 [CrossRef] [Google Scholar] [PubMed]
  32. El Bitar F, Meunier J, Villard V, Alméras M, Krishnan K, et al. (2014) Neuroprotection by the synthetic neurosteroid enantiomers ent-PREGS and ent-DHEAS against Aβ25-35 peptide-induced toxicity in vitro and in vivo in mice. Psychopharmacology (Berl) 231: 3293-3312 [CrossRef] [Google Scholar] [PubMed]
  33. Pertusa M, Garcia-Matas S, Rodriguez-Farre E, Sanfeliu C, Cristofol R, et al. (2007) Astrocytes aged in vitro show a decreased neuroprotective capacity. J Neurochem 101: 794-805 [CrossRef] [Google Scholar] [PubMed]
  34. Segovia G, Porras A, Del Arco A, Mora F (2001) Glutamatergic neurotransmission in aging: a critical perspective. Mech Ageing Dev 122: 1-29 [CrossRef] [Google Scholar] [PubMed]
  35. Dyall SC (2015) Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci 7: 52 [CrossRef] [Google Scholar] [PubMed]
  36. Gupta SC, Patchva S, Aggarwal BB (2013) Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 15: 195-218 [CrossRef] [Google Scholar] [PubMed]