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. 2020 Oct 15;11:538301. doi: 10.3389/fneur.2020.538301

Table 5.

Epigenetic therapeutic strategies in AD.

Therapeutic strategies Model Main findings References
Dnmt3a2 (DNA methyltransferase) Aged mice The raise Dnmt3a2 level in the hippocampus of aged mice enhanced cognitive ability (160)
Betaine(a methyl donor) Male ddY strain mice Betaine treatment ameliorate memory deficit (161)
S-adenosylmethionine(SAM, a methyl donor) TgCRND8 mice SAM reduced the Aβ production and improved the memory (162)
Alcohol extracts from G. lucidum APP/PS1 AD model mice It increased methylation regulators and improved memory (163)
B vitamin AD patients and mild cognitive impairment patients It resulted in hypermethylation of NUDT15 and TXNRD1 and better cognitive performance (164)
Folic acid Participants who tend to decline with age The supplementation of folic acid improved cognitive functions (165)
Resveratrol SAMP8 mice It promoted cognitive decline in the SAMP8 mice offspring (166)
UNC0642 5XFAD mouse model It inhibited the methyltransferase activity G9a/GLP and restored cognition (167)
Trichostatin A AD mouse model It restored contextual freezing performance (100)
Valproic acid (VPA, a histone deacetylase inhibitor) APPswe/PS1ΔE9 (APP/PS1) transgenic mice VPA decreased Aβ deposition and increased memory ability (168)
Sodium phenylbutyrate (a histone deacetylase inhibitor) 5XFAD mice Sodium phenylbutyrate improved memory and spatial learning (169)
M344 (a histone deacetylase inhibitor) Triple transgenic (APPsw/PS1M146V/TauP301L) mice M344 lowered the expression of Aβ and prevent cognitive decline (170)
Mercaptoacetamide-based class II HDACi and a hydroxamide-based class I and II HDACi 3xTg AD mice They reduced Aβ levels in vitro and rescued memory loss (171)
Vorinostat Primary human brain tissue It decreased PU.1 expression and was associated with lower AD risk (172)
RGFP-966 AD mice model It improved cognitive functions (173)
CBP/p300 (an activator of histone acetyltransferase) 3xTg-AD mice CBP/p300 extended the recent memory duration (174)
The inhibitors of euchromatic histone methyltransferases FAD mouse model It decreased histone hyper-methylation and cognitive functions (175)
Short-interfering RNA AD mice models It decreased the expression of BACE1 (176)
RNA interference AD mice models It downregulated the expression of APP, PSEN1, PSEN2 (177)
MicroRNA-384 mimic SH-SY5Y cells MicroRNA-384 mimic downregulated the expression of APP and BACE1 (178)
Anti-microRNA-146a-base treatment AD mouse model It improved cognitive functions in AD (179)
Inhibitor of microRNA-34c AD mice models It could enhance the memory ability (180)
Knockdown of BACE1-AS by lentivirus SAMP8 mice It improved learning behaviors and memory (145)
MicroRNA-124 SH-SY5Y cells It decreased apoptosis and decreased Aβ-induced viability inhibition (181)

HDACi, inhibitor of histone deacetylase; BACE1-AS, BACE1-antisense transcript; NUDT15, nudix hydrolase 15; TXNRD1, thioredoxin reductase 1.