Table 2.

List of potential of nutraceuticals that target the epigenetic machinery in neurodegenerative disorders.

Name	Epigenetic Factor	Disease	Mechanism	Effect	Clinical Trial
Resveratrol	SIRT1 Activator	PD Mitochondrial dysfunction   Abnormal protein deposition (α-synuclein)   AD ▪Tau phosphorylation and NFT deposition	AMPK-SIRT1 signaling pathway, inducing PGC-1 activity.   SIRT1 deacetylates heat shock factor 1 and increases the transcription of heat shock proteins (Hsp70s).     SIRT 1 deacetylates p53, reducing its expression, disturbing p53-GSK3β interaction.	Improves mitochondrial function [247].     Prevents the production of pathological protein aggregates [248].   Reduces tau phosphorylation and NFT deposition [249].
Curcumin           Theracurmin (90–180 mg/day)	p300/CBP HAT Inhibitor	AD ▪PS1 ▪BACE 1 ▪Aβ plaque deposition	Inhibiting H3 acetylation at the promoter of gene by inhibiting p300 HAT.	Supress PS1 and BACE 1 expression [250].       Reducing Aβ accumulation [251].	Phase II clinical trial (ClinicalTrials.gov Identifier: NCT01383161) [251]
Folic acid   Vit B9 Vit B6 Vit B12	Increase SAM	AD   AD PD PD	Upregulate Methylation of Aβ-40, PS1.	Reduces Aβ burden [252].   Downregulates cytokine expression [253]. Improves cognitive dysfunction [254].	(ChiCTR-TRC-13003246) [252]
EGCG	DNMT inhibitor   HDAC inhibitor	AD     SAMP8 mouse model of AD	Alters DNA methylation profile.     Decreases HDAC activity, increases H3 and H4 acetylation, and downregulates HDAC1, HDAC2, and G9a expression, respectively.	Prevention of Aβ aggregation in AD [255].   Facilitates the degradation of Aβ [256].	Phase II and III clinical trials (NTC00951834) [232]
AtreMorine	DNMT activator	Triple transgenic mouse model of AD	Upregulates DNMT3a and increases global DNA methylation.	Reduces plaque formation [257].
Nosustrophine	SIRT1 activator	AD	Deacetylation of H3K14.	Promotes survival by attenuating Bax-dependent apoptosis [258].