Phytochemicals as Regulators of Genes Involved in Synucleinopathies

Abstract

Synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of α-synuclein aggregates in neurons, nerve fibers or glial cells. Three main types of diseases belong to the synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. All of them develop as a result of an interplay of genetic and environmental factors. Emerging evidence suggests that epigenetic mechanisms play an essential role in the development of synucleinopathies. Since there is no disease-modifying treatment for these disorders at this time, interest is growing in plant-derived chemicals as a potential treatment option. Phytochemicals are substances of plant origin that possess biological activity, which might have effects on human health. Phytochemicals with neuroprotective activity target different elements in pathogenic pathways due to their antioxidants, anti-inflammatory, and antiapoptotic properties, and ability to reduce cellular stress. Multiple recent studies demonstrate that the beneficial effects of phytochemicals may be explained by their ability to modulate the expression of genes implicated in synucleinopathies and other diseases. These substances may regulate transcription directly via transcription factors (TFs) or play the role of epigenetic regulators through their effect on histone modification, DNA methylation, and RNA-based mechanisms. Here, we summarize new data about the impact of phytochemicals on the pathogenesis of synucleinopathies through regulation of gene expression.

Case Report: Synucleinopathy Associated With Phalaris Neurotoxicity in Sheep

“…Phytochemicals are structurally diverse biologically active compounds of plant origin that possess various beneficial and toxic properties toward synucleinopathies (21). Here, we describe the effect of alkaloids from Phalaris on the development of pathology in sheep.…”

Molecular Cloning and Identification of NADPH Cytochrome P450 Reductase from Panax ginseng

“…As a plant hormone, MeJA [30] can induce ginsenoside synthesis [31]. The content of PgCPR 1 and PgCPR 2 in the callus was detected by qPCR after being induced in a concentration-dependent manner for 24 h. The results showed that the expression of PgCPR1 and PgCPR2 increased significantly with the increase of MeJA concentration and reached the maximum value in 100 µM MeJA treatments, and then decreased significantly in the 150 µM MeJA treatment.…”

The Multifaceted Roles of Proline in Cell Behavior

“…Several metabolites may influence, directly or indirectly, the activity of chromatin-modifying enzymes, and thus the epigenetic landscape of the cells (Reid et al, 2017;D'Aniello et al, 2019b;Surguchov et al, 2021). L-Pro is not a substrate, product, cofactor, or allosteric regulator of any epigenetic enzyme, but in ESCs its availability influences the activity of ten-eleven translocation (TET; DNA) and Jumonji (JMJ, histone) demethylase enzymes, which are strictly dependent on the availability of O 2 , α-KG, and ascorbic acid (vitamin C, VitC) to be active (Figure 7; Comes et al, 2013;D'Aniello et al, 2016D'Aniello et al, , 2019b.…”