Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease.
AMP deaminase
fructokinase
fructose
mitochondria
sugar
uric acid
Journal
Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
05
2020
accepted:
24
08
2020
entrez:
7
10
2020
pubmed:
8
10
2020
medline:
8
10
2020
Statut:
epublish
Résumé
The loss of cognitive function in Alzheimer's disease is pathologically linked with neurofibrillary tangles, amyloid deposition, and loss of neuronal communication. Cerebral insulin resistance and mitochondrial dysfunction have emerged as important contributors to pathogenesis supporting our hypothesis that cerebral fructose metabolism is a key initiating pathway for Alzheimer's disease. Fructose is unique among nutrients because it activates a survival pathway to protect animals from starvation by lowering energy in cells in association with adenosine monophosphate degradation to uric acid. The fall in energy from fructose metabolism stimulates foraging and food intake while reducing energy and oxygen needs by decreasing mitochondrial function, stimulating glycolysis, and inducing insulin resistance. When fructose metabolism is overactivated systemically, such as from excessive fructose intake, this can lead to obesity and diabetes. Herein, we present evidence that Alzheimer's disease may be driven by overactivation of cerebral fructose metabolism, in which the source of fructose is largely from endogenous production in the brain. Thus, the reduction in mitochondrial energy production is hampered by neuronal glycolysis that is inadequate, resulting in progressive loss of cerebral energy levels required for neurons to remain functional and viable. In essence, we propose that Alzheimer's disease is a modern disease driven by changes in dietary lifestyle in which fructose can disrupt cerebral metabolism and neuronal function. Inhibition of intracerebral fructose metabolism could provide a novel way to prevent and treat this disease.
Identifiants
pubmed: 33024433
doi: 10.3389/fnagi.2020.560865
pmc: PMC7516162
doi:
Types de publication
Journal Article
Langues
eng
Pagination
560865Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK048520
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108408
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108859
Pays : United States
Informations de copyright
Copyright © 2020 Johnson, Gomez-Pinilla, Nagel, Nakagawa, Rodriguez-Iturbe, Sanchez-Lozada, Tolan and Lanaspa.
Références
Cell Metab. 2018 Feb 6;27(2):351-361.e3
pubmed: 29414685
J Neurochem. 2015 May;133(4):572-81
pubmed: 25708447
Nat Commun. 2013;4:2434
pubmed: 24022321
Am J Physiol. 1998 Mar;274(3):R746-53
pubmed: 9530242
Exp Diabetes Res. 2012;2012:789730
pubmed: 22110479
Sci Rep. 2016 Jun 09;6:27524
pubmed: 27276998
J Am Soc Nephrol. 2016 Aug;27(8):2247-56
pubmed: 27283495
Proc Natl Acad Sci U S A. 2015 May 19;112(20):6509-14
pubmed: 25941364
Neurobiol Learn Mem. 2014 Oct;114:10-5
pubmed: 24752150
JOP. 2001 Jul;2(4):124-39
pubmed: 11875249
JAMA Intern Med. 2014 Apr;174(4):516-24
pubmed: 24493081
PLoS One. 2015 Jun 15;10(6):e0130432
pubmed: 26075716
Oxid Med Cell Longev. 2015;2015:985845
pubmed: 25815110
Public Health Nutr. 2012 Oct;15(10):1925-31
pubmed: 22153053
Am J Physiol. 1971 Dec;221(6):1629-39
pubmed: 5124307
EBioMedicine. 2016 May;7:157-66
pubmed: 27322469
Behav Brain Res. 2016 Jun 1;306:1-7
pubmed: 26970578
Biochim Biophys Acta. 2015 Nov;1852(11):2379-90
pubmed: 26300486
Am J Nephrol. 2011;34(1):49-54
pubmed: 21659739
Lancet. 2011 Jul 30;378(9789):380-2
pubmed: 21803192
Biomolecules. 2019 Oct 11;9(10):
pubmed: 31614639
Diabetes Care. 2003 Jul;26(7):1961-6
pubmed: 12832296
J Am Soc Nephrol. 2010 Sep;21(9):1543-9
pubmed: 20595676
Annu Rev Nutr. 2006;26:1-22
pubmed: 16848698
PLoS One. 2017 Feb 23;12(2):e0172645
pubmed: 28231304
Eur J Neurol. 2016 May;23(5):948-57
pubmed: 26917248
J Biol Chem. 1997 Jun 27;272(26):16431-7
pubmed: 9195951
Age (Dordr). 2016 Feb;38(1):16
pubmed: 26820749
Nutrients. 2015 Aug 12;7(8):6719-38
pubmed: 26274972
PLoS One. 2012;7(11):e48801
pubmed: 23152807
Nat Rev Rheumatol. 2020 Feb;16(2):75-86
pubmed: 31822862
Diabetes. 2013 Oct;62(10):3307-15
pubmed: 24065788
J Diabetes Complications. 1996 Mar-Apr;10(2):109-12
pubmed: 8777329
Brain Res. 2017 Feb 15;1657:312-322
pubmed: 28034722
Nutrients. 2018 May 04;10(5):
pubmed: 29734664
J Clin Endocrinol Metab. 2005 Feb;90(2):1171-5
pubmed: 15562012
Metabolism. 2012 May;61(5):641-51
pubmed: 22152650
J Biol Chem. 1966 Dec 25;241(24):5819-26
pubmed: 4380931
Mayo Clin Womens Healthsource. 2005 Nov;9(11):3
pubmed: 16224362
PLoS One. 2012;7(10):e47948
pubmed: 23112875
Science. 2009 Feb 20;323(5917):1063-6
pubmed: 19229036
Science. 2017 Apr 21;356(6335):307-311
pubmed: 28428423
J Neuropathol Exp Neurol. 2001 Jul;60(7):686-95
pubmed: 11444797
NMR Biomed. 1991 Feb;4(1):38-40
pubmed: 1903044
Lancet. 2017 Nov 25;390(10110):2327-2329
pubmed: 29185425
Biochem J. 1977 Mar 15;162(3):601-9
pubmed: 869906
Clin Interv Aging. 2019 Jul 22;14:1331-1342
pubmed: 31413554
Public Health Nutr. 2012 Mar;15(3):433-41
pubmed: 21929845
J Nutr. 2013 Sep;143(9):1406-13
pubmed: 23864508
Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):9080-9085
pubmed: 28784767
Nature. 2019 Oct;574(7780):686-690
pubmed: 31645758
Alzheimers Dement. 2017 Sep;13(9):955-964
pubmed: 28274718
Metabolism. 2011 Sep;60(9):1259-70
pubmed: 21489572
Semin Nephrol. 2005 Jan;25(1):3-8
pubmed: 15660328
Biol Psychiatry. 2014 Jan 1;75(1):31-7
pubmed: 23582268
Mol Med Rep. 2017 Sep;16(3):2767-2772
pubmed: 28677809
Neuroepidemiology. 2013;41(1):29-34
pubmed: 23548762
Am J Hypertens. 2020 Jul 18;33(7):583-594
pubmed: 32179896
Cell Metab. 2019 Oct 1;30(4):735-753.e4
pubmed: 31577934
Arch Int Physiol Biochim Biophys. 1991 Dec;99(6):455-60
pubmed: 1725750
Clin J Am Soc Nephrol. 2016 Jun 6;11(6):1015-23
pubmed: 27026520
Nat Commun. 2017 Feb 13;8:14181
pubmed: 28194018
Arthritis Res Ther. 2015 May 28;17:139
pubmed: 26018424
JCI Insight. 2017 Feb 23;2(4):e90508
pubmed: 28239653
Oncotarget. 2017 Sep 27;8(56):95780-95790
pubmed: 29221166
Neuropsychology. 2007 Jan;21(1):136-40
pubmed: 17201536
J Acad Nutr Diet. 2012 Nov;112(11):1828-34.e1-6
pubmed: 23102182
J Infect Dis. 2020 Mar 16;221(7):1088-1097
pubmed: 31665341
J Clin Endocrinol Metab. 2011 Dec;96(12):E2034-8
pubmed: 21956423
Biomed Res Int. 2014;2014:908915
pubmed: 25089278
J Cereb Blood Flow Metab. 2016 May;36(5):941-53
pubmed: 26661172
Free Radic Biol Med. 2019 Sep;141:182-191
pubmed: 31212064
Mol Cell. 2016 Mar 3;61(5):654-666
pubmed: 26942670
Prog Neurobiol. 2018 Oct;169:76-90
pubmed: 30059718
J Biol Chem. 2012 Nov 23;287(48):40732-44
pubmed: 23035112
Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1370-5
pubmed: 18703413
Mol Nutr Food Res. 2017 Oct;61(10):
pubmed: 28654221
Front Physiol. 2015 Jan 14;5:522
pubmed: 25642192
Diabetes. 2010 Jan;59(1):4-5
pubmed: 20040482
Clin Geriatr Med. 2018 Nov;34(4):617-635
pubmed: 30336991
Drug News Perspect. 2007 Nov;20(9):573-8
pubmed: 18176662
Cancer Metab. 2020 Jul 10;8:16
pubmed: 32670573
Neurology. 2007 Oct 2;69(14):1418-23
pubmed: 17909154
J Clin Hypertens (Greenwich). 2018 Oct;20(10):1447-1454
pubmed: 30232829
Physiol Behav. 2015 Dec 1;152(Pt B):363-71
pubmed: 26066731
Am J Prev Med. 2018 Jun;54(6):727-735
pubmed: 29674185
J Neural Transm Park Dis Dement Sect. 1991;3(1):1-14
pubmed: 1905936
Nature. 2015 Jun 25;522(7557):444-449
pubmed: 26083752
Neuroscience. 2006 Jul 7;140(3):889-95
pubmed: 16581195
Front Aging Neurosci. 2017 Oct 31;9:345
pubmed: 29163128
Hippocampus. 2015 Feb;25(2):227-39
pubmed: 25242636
Am J Physiol Endocrinol Metab. 2018 Aug 1;315(2):E141-E149
pubmed: 29634315
J Am Soc Nephrol. 2002 Dec;13(12):2888-97
pubmed: 12444207
Neurobiol Aging. 1998 Sep-Oct;19(5):385-91
pubmed: 9880040
Front Pharmacol. 2019 Aug 23;10:902
pubmed: 31507410
Neurobiol Dis. 2020 Apr;137:104739
pubmed: 31927145
Cureus. 2018 May 21;10(5):e2660
pubmed: 30042911
Nutrients. 2017 Jun 16;9(6):
pubmed: 28621759
Pharmacol Biochem Behav. 1989 Jun;33(2):367-9
pubmed: 2813475
Neuroscience. 2015 Aug 20;301:213-20
pubmed: 26079112
Mol Nutr Food Res. 2019 Aug;63(15):e1801054
pubmed: 31087499
Brain. 2009 Feb;132(Pt 2):377-82
pubmed: 19036766
Alcohol Alcohol. 2017 Mar 9;52(2):158
pubmed: 28182204
Neurobiol Aging. 2011 Nov;32(11):1932-41
pubmed: 20045217
Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3138-3143
pubmed: 29507217
J Biol Chem. 2019 Mar 15;294(11):4272-4281
pubmed: 30651350
Neural Regen Res. 2019 May;14(5):749-756
pubmed: 30688256
Am J Physiol Renal Physiol. 2006 Mar;290(3):F625-31
pubmed: 16234313
J Physiol. 2012 May 15;590(10):2485-99
pubmed: 22473784
PLoS One. 2014 Apr 15;9(4):e95019
pubmed: 24736531
Neurodegener Dis. 2013;12(4):189-98
pubmed: 23467193
Am J Physiol Renal Physiol. 2016 Oct 1;311(4):F722-F730
pubmed: 27465991
Brain Res Brain Res Rev. 2002 Jun;39(1):55-73
pubmed: 12086708
Curr Opin Clin Nutr Metab Care. 2013 Jul;16(4):440-5
pubmed: 23657152
Nutrients. 2013 Jul 26;5(8):2901-23
pubmed: 23896654
Clin Nutr. 2016 Jun;35(3):645-9
pubmed: 25935852
J Cell Physiol. 2017 May;232(5):1069-1078
pubmed: 27474828
J Alzheimers Dis. 2015;44(2):649-60
pubmed: 25322927
Carcinogenesis. 2017 Feb 1;38(2):119-133
pubmed: 27993896
Obesity (Silver Spring). 2019 Jun;27(6):879-887
pubmed: 31054268
PLoS Genet. 2014 Sep 04;10(9):e1004606
pubmed: 25188341
Obesity (Silver Spring). 2013 Apr;21(4):659-64
pubmed: 23401356
J Am Coll Cardiol. 2015 Oct 6;66(14):1615-1624
pubmed: 26429086
Front Mol Neurosci. 2016 Aug 08;9:57
pubmed: 27551259
Nat Cell Biol. 2009 Jun;11(6):747-52
pubmed: 19448625
Kidney Int. 2012 Feb;81(4):407-11
pubmed: 22048126
Int J Biol Sci. 2017 Jul 18;13(8):961-975
pubmed: 28924378
Arch Neurol. 2006 Sep;63(9):1312-7
pubmed: 16966511
J Neurol. 1988 Jan;235(3):143-8
pubmed: 3367161
Ann Neurol. 2013 Oct;74(4):517-26
pubmed: 23794448
J Alzheimers Dis. 2012;32(2):329-39
pubmed: 22810099
Neurobiol Aging. 2020 Jun;90:60-74
pubmed: 31879131
FASEB J. 2014 Aug;28(8):3339-50
pubmed: 24755741
Biochem Biophys Res Commun. 2009 Apr 24;382(1):1-5
pubmed: 19265677
J Neurosci. 2016 Oct 26;36(43):10990-11005
pubmed: 27798180
Cell Metab. 2016 Feb 9;23(2):344-9
pubmed: 26724861
Hepatology. 2020 Feb 22;:
pubmed: 32086945
Gerontology. 1984;30(3):159-66
pubmed: 6373505
Hypertension. 2014 Mar;63(3):e68-73
pubmed: 24379189
J Histochem Cytochem. 2009 Aug;57(8):763-74
pubmed: 19365088
J Neurosci. 2014 Feb 12;34(7):2464-70
pubmed: 24523537
Arch Neurol. 2004 May;61(5):661-6
pubmed: 15148141
Neurobiol Aging. 2016 Aug;44:138-142
pubmed: 27318141
Mol Chem Neuropathol. 1992 Jun;16(3):207-24
pubmed: 1418218
Learn Mem. 2015 Mar 16;22(4):215-24
pubmed: 25776039
Diabetes Obes Metab. 2011 Mar;13(3):229-34
pubmed: 21205113
J Neurochem. 1967 Nov;14(11):1057-66
pubmed: 6058523
Exp Clin Endocrinol Diabetes. 2013 Oct;121(9):535-8
pubmed: 23934680
Appetite. 2014 Jun;77:1-12
pubmed: 24582585
Br J Nutr. 2011 Nov;106(9):1423-32
pubmed: 21736803
Nutr Neurosci. 2012 May;15(3):127-33
pubmed: 22334236
Postgrad Med. 2011 Sep;123(5):39-49
pubmed: 21904085
Science. 2019 Mar 22;363(6433):1345-1349
pubmed: 30898933
J Nutr Health Aging. 2015 Apr;19(4):413-23
pubmed: 25809805
Nat Rev Neurol. 2018 Mar;14(3):168-181
pubmed: 29377010
Lancet. 1967 Sep 9;2(7515):528-31
pubmed: 4166890
Neurology. 2013 Apr 23;80(17):1557-64
pubmed: 23535495
J Neurophysiol. 2017 Feb 1;117(2):646-654
pubmed: 27852737
Science. 1968 Sep 20;161(3847):1253-4
pubmed: 5673437
Arthritis Res Ther. 2018 Aug 3;20(1):167
pubmed: 30075731
J Intern Med. 2020 Mar;287(3):252-262
pubmed: 31621967
Front Neurosci. 2019 Jul 26;13:763
pubmed: 31404153
Acta Neuropathol. 2018 Nov;136(5):663-689
pubmed: 30349969
Neurosci Lett. 1990 Sep 18;117(3):358-62
pubmed: 2094824
Nephron Exp Nephrol. 2012;121(3-4):e71-8
pubmed: 23235493
Am J Clin Nutr. 2017 Dec;106(6):1463-1470
pubmed: 29070566
Arch Neurol. 2005 Jan;62(1):55-60
pubmed: 15642850
Drugs. 2017 Jan;77(1):47-65
pubmed: 27988872