Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease

Vishweswaraiah, Sangeetha; Akyol, Sümeyya; Yılmaz, Ali; Ugur, Zafer; Gordevičius, Juozas; Oh, Kyung Joon; Brundin, Patrik; Radhakrishna, Uppala; Labrie, Viviane; Graham, Stewart F.

doi:10.3389/fnins.2022.804261

Cited by 6 publications

(3 citation statements)

References 64 publications

(70 reference statements)

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“…Our results have shown no significant correlation between PWY-5913 and significantly different microbes, which indicated that this different pathway uncovered a whole-level difference. Meanwhile, CYP39A1 encoded a member of the cytochrome P450 superfamily of enzymes and played an important role in tumor progression ( Khenjanta et al, 2014 ; Ji et al, 2022 ) and neurodegenerative disorder ( Vishweswaraiah et al, 2022 ). CYP39A1 might affect a variety of microbes and finally show the difference in the PWY-5913 pathways.…”

Section: Discussionmentioning

confidence: 99%

The host genetics affects gut microbiome diversity in Chinese depressed patients

Han

Ji²,

Wang³

et al. 2023

Front. Genet.

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The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. Actinobacteria and Pseudomonades were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 (p = 8.65 × 10–9), Actinobacteria and rs77379751 (p = 8.56 × 10–9), and PWY-5913 and rs1775633082 (p = 4.54 × 10–8). A species of the Romboutsia genus was co-associated with the species of Ruminococcus gnavus in an internetwork through four genes: METTL8, ITGB2, OTULIN, and PROSER3, with a strict threshold (p < 5 × 10–4). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced SERPINA5 and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.

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Section: Discussionmentioning

confidence: 99%

The host genetics affects gut microbiome diversity in Chinese depressed patients

Han

Ji²,

Wang³

et al. 2023

Front. Genet.

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“…Several of the aforementioned studies used Gene Ontology analysis to examine the functions of genes with altered methylation. Some of the key processes affected were neuronal development and differentiation, synaptic transmission, neurotransmitter transport, dopaminergic synapse, metabolism, immunity, bile acid secretion, cell cycle and cell signaling (including the Wnt pathway), all of which have been implicated in PD pathogenesis [ 87 , 91 , 93 , 94 , 98 , 101 ].…”

Section: Dna Methylationmentioning

confidence: 99%

An Overview of Epigenetic Changes in the Parkinson’s Disease Brain

Klokkaris,

Migdalska-Richards

2024

IJMS

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Parkinson’s disease is a progressive neurodegenerative disorder, predominantly of the motor system. Although some genetic components and cellular mechanisms of Parkinson’s have been identified, much is still unknown. In recent years, emerging evidence has indicated that non-DNA-sequence variation (in particular epigenetic mechanisms) is likely to play a crucial role in the development and progression of the disease. Here, we present an up-to-date overview of epigenetic processes including DNA methylation, DNA hydroxymethylation, histone modifications and non-coding RNAs implicated in the brain of those with Parkinson’s disease. We will also discuss the limitations of current epigenetic research in Parkinson’s disease, the advantages of simultaneously studying genetics and epigenetics, and putative novel epigenetic therapies.

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“…In early PD, accelerated hematopoietic cell mitosis was revealed, possibly reflecting immune pathway imbalances, which may be related to motor and cognitive progression [ 64 ]. The integration of metabolomics and epigenetics (genome-wide DNA methylation; epimetabolomics) was described after studies of the frontal lobe of people who died from PD: 48 metabolites and 4313 differentially methylated sites were identified in the primary motor cortex of people who died from PD, as compared with age- and sex-matched controls [ 65 ]. The metabolite taurine level correlated with CpG methylated sites, and bile acid biosynthesis was the major biochemical pathway to be perturbed in the frontal lobe of PD sufferers.…”

Section: Familial and Sporadic Forms Of Pd Epigenetic Aspectsmentioning

confidence: 99%

Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease

Dolgacheva

Зинченко

Гончаров

2022

IJMS

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An increasing number of the population all around the world suffer from age-associated neurodegenerative diseases including Parkinson’s disease (PD). This disorder presents different signs of genetic, epigenetic and environmental origin, and molecular, cellular and intracellular dysfunction. At the molecular level, α-synuclein (αSyn) was identified as the principal molecule constituting the Lewy bodies (LB). The gut microbiota participates in the pathogenesis of PD and may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The most important pathogenetic link is an imbalance of Ca2+ ions, which is associated with redox imbalance in the cells and increased generation of reactive oxygen species (ROS). In this review, genetic, epigenetic and environmental factors that cause these disorders and their cause-and-effect relationships are considered. As a constituent of environmental factors, the example of organophosphates (OPs) is also reviewed. The role of endothelial damage in the pathogenesis of PD is discussed, and a ‘triple hit hypothesis’ is proposed as a modification of Braak’s dual hit one. In the absence of effective therapies for neurodegenerative diseases, more and more evidence is emerging about the positive impact of nutritional structure and healthy lifestyle on the state of blood vessels and the risk of developing these diseases.

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Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease

Cited by 6 publications

References 64 publications

The host genetics affects gut microbiome diversity in Chinese depressed patients

The host genetics affects gut microbiome diversity in Chinese depressed patients

An Overview of Epigenetic Changes in the Parkinson’s Disease Brain

Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease

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