title: Cocoa powder triggers neuroprotective and preventive effects in a human Alzheimer's disease model by modulating BDNF signaling pathway.
abstract: The molecular mechanisms linking Aβ to the onset of neurotoxicity are still largely unknown, but several lines of evidence point to reactive oxygen species, which are produced even under the effect of nanomolar concentrations of soluble Aβ-oligomers. The consequent oxidative stress is considered as the mediator of a cascade of degenerative events in many neurological disorders. Epidemiological studies indicate that dietary habits and antioxidants from diet can influence the incidence of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In the recent years, a number of reviews have reported on neuroprotective effects of polyphenols in cell and animal models. However, the majority of these studies have focused only on the anti-oxidant properties of these compounds and less on the mechanism/s of action at cellular level. In this work we investigated the effect of cocoa polyphenolic extract on a human AD in vitro model. The results obtained, other than confirming the anti-oxidant properties of cocoa, demonstrate that cocoa polyphenols triggers neuroprotection by activating BDNF survival pathway, both on Aβ plaque treated cells and on Aβ oligomers treated cells, resulting in the counteraction of neurite dystrophy. On the light of the results obtained the use of cocoa powder as preventive agent for neurodegeneration is further supported.
authors.affiliation: Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy. annamaria.cimini@univaq.it
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cimini
authors.forename: Roberta
authors.initials: R
authors.lastname: Gentile
authors.forename: Barbara
authors.initials: B
authors.lastname: D'Angelo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Benedetti
authors.forename: Loredana
authors.initials: L
authors.lastname: Cristiano
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Avantaggiati
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferri
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Desideri
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000517:prevention & control*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002099:Cacao / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010936:Plant Extracts; D059808:Polyphenols
keywords: ANTI-OXIDANT; BDNF SIGNALING; CYTOSKELETRIC PROTEINS; NEURITES; NEURODEGENERATIVE DISEASES; NEURONS
references.citation: Nutr Rev. 1998 Nov;56(11):317-33
references.pmid: 9838798
references.citation: Free Radic Biol Med. 1997;23(1):134-47
references.pmid: 9165306
references.citation: Clin Interv Aging. 2007;2(2):219-36
references.pmid: 18044138
references.citation: Free Radic Biol Med. 2004 Aug 1;37(3):304-17
references.pmid: 15223064
references.citation: Neurosci Lett. 1996 Oct 18;217(2-3):210-1
references.pmid: 8916111
references.citation: Free Radic Res. 2004 Aug;38(8):771-85
references.pmid: 15493450
references.citation: Free Radic Biol Med. 2012 Jan 1;52(1):35-45
references.pmid: 21982844
references.citation: Life Sci. 2001 Dec 21;70(5):603-14
references.pmid: 11811904
references.citation: Pathol Biol (Paris). 1996 Jan;44(1):57-64
references.pmid: 8734302
references.citation: Neurotox Res. 2003;5(6):425-32
references.pmid: 14715446
references.citation: J Agric Food Chem. 2008 Jul 9;56(13):4855-73
references.pmid: 18557624
references.citation: Neurobiol Dis. 2005 Apr;18(3):459-65
references.pmid: 15755672
references.citation: J Neurochem. 2007 Jun;101(6):1596-606
references.pmid: 17298385
references.citation: Science. 2002 Oct 25;298(5594):789-91
references.pmid: 12399581
references.citation: J Alzheimers Dis. 2009;18(4):935-52
references.pmid: 19749434
references.citation: Annu Rev Nutr. 2002;22:19-34
references.pmid: 12055336
references.citation: J Neurosci. 2005 Jun 1;25(22):5455-63
references.pmid: 15930396
references.citation: JAMA. 2002 Jun 26;287(24):3223-9
references.pmid: 12076218
references.citation: Lancet. 1996 Sep 21;348(9030):834
references.pmid: 8814019
references.citation: Chem Res Toxicol. 1997 May;10(5):518-26
references.pmid: 9168248
references.citation: Lab Invest. 1991 Jul;65(1):104-10
references.pmid: 1906561
references.citation: J Biol Chem. 2006 Jul 21;281(29):20315-25
references.pmid: 16714296
references.citation: J Nutr. 2000 Aug;130(8S Suppl):2086S-92S
references.pmid: 10917927
references.citation: Cell Biophys. 1989 Apr;14(2):175-85
references.pmid: 2472207
references.citation: Hypertension. 2012 Sep;60(3):794-801
references.pmid: 22892813
references.citation: J Nutr. 2004 Oct;134(10):2509-16
references.pmid: 15465739
references.citation: J Neurochem. 2007 Jun;101(5):1172-84
references.pmid: 17286590
references.citation: Mol Neurobiol. 2005;31(1-3):135-47
references.pmid: 15953817
references.citation: FEBS Lett. 1999 May 7;450(3):205-9
references.pmid: 10359075
references.citation: J Agric Food Chem. 2003 Dec 3;51(25):7292-5
references.pmid: 14640573
references.citation: J Nutr Biochem. 2008 Sep;19(9):619-26
references.pmid: 18280729
references.citation: J Am Diet Assoc. 2003 Feb;103(2):215-23
references.pmid: 12589329
references.citation: Arch Neurol. 1997 Jun;54(6):762-5
references.pmid: 9193212
references.citation: J Struct Biol. 2000 Jun;130(2-3):184-208
references.pmid: 10940225
references.citation: Neuroepidemiology. 2001 Feb;20(1):7-15
references.pmid: 11174040
references.citation: Neurology. 1995 Aug;45(8):1594-601
references.pmid: 7644059
references.citation: J Nutr. 2001 Mar;131(3):834-5
references.pmid: 11238767
references.citation: Eur J Epidemiol. 2000 Apr;16(4):357-63
references.pmid: 10959944
references.citation: PLoS One. 2009;4(2):e4606
references.pmid: 19242551
references.citation: Exp Neurol. 1998 Mar;150(1):40-4
references.pmid: 9514828
references.citation: J Neurosci. 1999 Mar 15;19(6):1959-64
references.pmid: 10066249
references.citation: Eur J Pharmacol. 2006 Sep 1;545(1):51-64
references.pmid: 16904103
references.citation: Arch Neurol. 1998 Nov;55(11):1409-15
references.pmid: 9823823
references.citation: Am J Clin Nutr. 2000 Feb;71(2):621S-629S
references.pmid: 10681270
references.citation: J Agric Food Chem. 2005 Mar 9;53(5):1445-8
references.pmid: 15740021
references.citation: Neurotox Res. 2006 Aug;10(1):23-30
references.pmid: 17000467
references.citation: Neuron. 1996 Apr;16(4):881-91
references.pmid: 8608006
references.citation: J Biol Chem. 2005 Dec 9;280(49):41057-68
references.pmid: 16204253
references.citation: J Neurochem. 2010 Mar;112(6):1415-30
references.pmid: 20050972
references.citation: Curr Med Chem. 2001 Jun;8(7):797-807
references.pmid: 11375750
references.citation: FASEB J. 2007 Nov;21(13):3511-21
references.pmid: 17595348
references.citation: Am J Clin Nutr. 2005 Jan;81(1 Suppl):313S-316S
references.pmid: 15640496
references.citation: J Am Chem Soc. 2001 Jun 20;123(24):5625-31
references.pmid: 11403592
references.citation: Nat Cell Biol. 2004 Nov;6(11):1054-61
references.pmid: 15516999
references.citation: Curr Alzheimer Res. 2009 Jun;6(3):238-51
references.pmid: 19519305