Daijiro Yanagisawa, Hamizah Shahirah Hamezah, Lina Wati Durani, Hiroyasu Taguchi, Ikuo Tooyama
Intracellular inclusions of aggregated tau appear in neurons and glial cells in a range of neurodegenerative diseases known as tauopathies. Inhibition of pathological changes in tau is a therapeutic target for tauopathy. We recently synthesized a novel curcumin derivative, named Shiga-Y5, and showed that Shiga-Y5 inhibited cognitive impairment and amyloid deposition in a mouse model of Alzheimer's disease. Here we investigated whether Shiga-Y5 inhibited cognitive impairment and tau accumulation in a mouse model of tauopathy, rTg4510. The rTg4510 mouse is a bitransgenic mouse model that uses a system of responder and activator transgenes to express human four-repeat tau with the P301L mutation. This strain is obtained by crossing tetO-MAPT*P301L mouse line (on a FVB/NJ background) with CaMKII-tTA mouse line (on a C57BL/6J background). Male rTg4510 mice and wild-type mice were fed with a standard chow diet with or without Shiga-Y5 (500 ppm) for 4 months. Behavioral tests were conducted from 5.5 months of age, and the mice were sacrificed at 6 months of age. There were no significant changes in behavioral performance in rTg4510 mice fed with SY5-containing chow diet compared with rTg4510 mice fed with control chow diet. Histological and biochemical analyses also showed no significant alterations in tau accumulation by the treatment with SY5. One of noticeable finding in this study was that rTg4510 mice on a F1 female FVB/NJ x male C57BL/6J background showed more severe tau accumulation than rTg4510 mice on a F1 female C57BL/6J x male FVB/NJ background. Further studies to clarify the mechanisms underlying tau aggregation may help to develop therapeutic approaches aimed at preventing this pathological feature.
J Alzheimers Dis. 2017;59(1):313-328
[PMID:
28598836]
PLoS One. 2015 Feb 06;10(2):e0117511
[PMID:
25659102]
Nat Rev Neurol. 2016 Jan;12(1):15-27
[PMID:
26635213]
Biomaterials. 2010 May;31(14):4179-85
[PMID:
20181392]
Cell Mol Life Sci. 2008 Jun;65(11):1631-52
[PMID:
18324353]
PLoS One. 2015 May 01;10(5):e0125614
[PMID:
25933020]
Neurosci Lett. 2014 Mar 6;562:63-8
[PMID:
24462887]
J Neurochem. 2007 Aug;102(4):1095-104
[PMID:
17472706]
Mol Neurodegener. 2014 Jan 15;9:8
[PMID:
24428919]
J Neuropathol Exp Neurol. 2010 Apr;69(4):405-14
[PMID:
20448485]
Nature. 1998 Jun 18;393(6686):702-5
[PMID:
9641683]
J Biol Chem. 2013 Feb 8;288(6):4056-65
[PMID:
23264626]
Neuron. 2012 Feb 23;73(4):685-97
[PMID:
22365544]
Science. 2005 Jul 15;309(5733):476-81
[PMID:
16020737]
Acta Neuropathol. 2017 May;133(5):665-704
[PMID:
28386764]
Nat Commun. 2015 Dec 16;6:10216
[PMID:
26671725]
Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006247
[PMID:
22762014]
Nat Protoc. 2006;1(2):848-58
[PMID:
17406317]
Trends Mol Med. 2009 Mar;15(3):112-9
[PMID:
19246243]
Neurobiol Aging. 2011 Apr;32(4):590-603
[PMID:
19427061]
Am J Pathol. 2009 Dec;175(6):2557-65
[PMID:
19893028]
J Neurosci Res. 2004 Mar 15;75(6):742-50
[PMID:
14994335]
Nat Rev Neurosci. 2007 Sep;8(9):663-72
[PMID:
17684513]
J Pharmacol Exp Ther. 2008 Jul;326(1):196-208
[PMID:
18417733]
Neurobiol Aging. 2014 Jul;35(7):1769-77
[PMID:
24503275]
Brain. 2016 May;139(Pt 5):1568-86
[PMID:
27020329]
J Neurosci. 2012 Aug 1;32(31):10574-86
[PMID:
22855807]
Nat Rev Neurosci. 2016 Jan;17(1):5-21
[PMID:
26631930]
Am J Pathol. 2006 May;168(5):1598-607
[PMID:
16651626]
J Neurosci. 2005 Nov 16;25(46):10637-47
[PMID:
16291936]
Neurobiol Aging. 2015 Jan;36(1):201-10
[PMID:
25179227]
Alzheimers Res Ther. 2017 Sep 20;9(1):77
[PMID:
28931441]
PLoS One. 2014 Aug 25;9(8):e106050
[PMID:
25153994]
J Neurosci Res. 2018 May;96(5):841-851
[PMID:
29063641]
Neuroscience. 2011 Jun 16;184:120-7
[PMID:
21497641]
J Neurosci. 2001 Nov 1;21(21):8370-7
[PMID:
11606625]
J Biol Chem. 2005 Feb 18;280(7):5892-901
[PMID:
15590663]
Neurobiol Aging. 2016 Mar;39:69-81
[PMID:
26923403]
Biochem Pharmacol. 2008 Feb 15;75(4):787-809
[PMID:
17900536]
