Role of Epigenetic Modulation in Neurodegenerative Diseases: Implications of Phytochemical Interventions

Abstract

Epigenetics defines changes in cell function without involving alterations in DNA sequence. Neuroepigenetics bridges neuroscience and epigenetics by regulating gene expression in the nervous system and its impact on brain function. With the increase in research in recent years, it was observed that alterations in the gene expression did not always originate from changes in the genetic sequence, which has led to understanding the role of epigenetics in neurodegenerative diseases (NDDs) including Alzheimer's disease (AD) and Parkinson's disease (PD). Epigenetic alterations contribute to the aberrant expression of genes involved in neuroinflammation, protein aggregation, and neuronal death. Natural phytochemicals have shown promise as potential therapeutic agents against NDDs because of their antioxidant, anti-inflammatory, and neuroprotective effects in cellular and animal models. For instance, resveratrol (grapes), curcumin (turmeric), and epigallocatechin gallate (EGCG; green tea) exhibit neuroprotective effects through their influence on DNA methylation patterns, histone acetylation, and non-coding RNA expression profiles. Phytochemicals also aid in slowing disease progression, preserving neuronal function, and enhancing cognitive and motor abilities. The present review focuses on various epigenetic modifications involved in the pathology of NDDs, including AD and PD, gene expression regulation related to epigenetic alterations, and the role of specific polyphenols in influencing epigenetic modifications in AD and PD.

Keywords: Alzheimer’s disease; Parkinson’s disease; epigenetic modulation; nutriepigenomics; phytochemicals; polyphenols.

Figure 1

Illustration of essential epigenetic mechanisms governing gene expression by regulating transcriptional activation and repression. (a) DNA methylation/demethylation involves adding or removing methyl groups to DNA, respectively, particularly at CpG dinucleotides, influencing gene silencing or activation. (b) Histone modifications, including acetylation/deacetylation and methylation/demethylation, modulate chromatin structure, promoting either transcriptional activation or repression. (c) Additionally, non-coding RNAs (ncRNAs) such as miRNA, circRNA, and lncRNA participate in fine-tuning gene expression by targeting mRNA stability or acting as molecular decoys.

Figure 2

Pathophysiological changes occurring during Alzheimer’s disease (created with BioRender.com).

Figure 3

Neurobiological mechanisms involved in the pathogenesis of Parkinson’s disease (created with BioRender.com).

Figure 4

Mechanism of phytochemicals in the regulation of epigenetic modifications in (A) Alzheimer’s Disease and (B) Parkinson’s Disease (created with BioRender.com).