Figure - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Source publication
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 p...
Context in source publication
Citations
... Similarly, epigenetic alterations in dopamine-related pathways contribute to the loss of dopaminergic neurons in PD. The disruption of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) further exacerbates neuronal signaling deficits, intensifying neurodegeneration [9]. ...
Epigenetic modulation plays a crucial role in neuroprotection by regulating cellular responses to stress, inflammation, and oxidative damage, particularly in neurodegenerative diseases. Recognizing the therapeutic potential of epigenetic regulators, this study investigated the synergistic neuroprotective effects of curcumin-enriched turmeric extract combined with L-ascorbic acid, focusing on its modulation of epigenetic pathways in oxidative stress-induced neuronal damage. SH-SY5Y neuronal cells were treated with the combination at 20 and 40 µg/mL, and subsequently exposed to 200 µM hydrogen peroxide (H2O2) to induce oxidative stress. Cell viability was assessed using the MTT assay, while neuroprotective mechanisms were evaluated by analyzing the markers of epigenetic modulation, oxidative stress, inflammation, and apoptosis. The combination significantly enhanced cell viability, upregulated sirtuin-1 (SIRT1), and reduced DNA methyltransferase 1 (DNMT1) expression, indicating effective epigenetic modulation. Enhanced antioxidant defenses were observed, as evidenced by increased activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), along with decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels, alleviating oxidative stress. Additionally, it suppressed nuclear factor kappa B (NF-κB) activity and its downstream mediator interleukin-6 (IL-6), thereby mitigating inflammation. The treatment also increased anti-apoptotic Bcl-2 expression while reducing pro-apoptotic markers, including caspase-3 and caspase-9, suggesting inhibition of the intrinsic apoptotic pathway. These findings highlight the novel neuroprotective effects of this combination, demonstrating its ability to modulate epigenetic pathways while reducing oxidative stress, suppressing inflammation, and preventing undesired apoptosis. Its multifaceted neuroprotective properties make it a promising functional ingredient in functional foods for neurodegenerative disease intervention. However, further investigations, including animal studies and clinical trials, are essential to evaluate its safety and therapeutic potential.
... Otherwise, a polymorphism of the PARK16 gene was associated with an increased risk of PD only in male subjects. Several reports highlight that epigenetic mechanisms may play a pivotal role in the etiology of PD, although the role of sex has been often overlooked [137]. Following is reported some evidence that epigenetic mechanisms are altered in PD in a sex-specific manner (summarized in Table 2). ...
Neurodegenerative diseases are characterized by profound differences between females and males in terms of incidence, clinical presentation, and disease progression. Furthermore, there is evidence suggesting that differences in sensitivity to medical treatments may exist between the two sexes. Although the role of sex hormones and sex chromosomes in driving differential susceptibility to these diseases is well-established, the molecular alterations underlying these differences remain poorly understood. Epigenetic mechanisms, including DNA methylation, histone tail modifications, and the activity of non-coding RNAs, are strongly implicated in the pathogenesis of neurodegenerative diseases. While it is known that epigenetic mechanisms play a crucial role in sexual differentiation and that distinct epigenetic patterns characterize females and males, sex-specific epigenetic patterns have been largely overlooked in studies aiming to identify epigenetic alterations associated with neurodegenerative diseases. This review aims to provide an overview of sex differences in epigenetic mechanisms, the role of sex-specific epigenetic processes in the central nervous system, and the main evidence of sex-specific epigenetic alterations in three neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Understanding the sex-related differences of these diseases is essential for developing personalized treatments and interventions that account for the unique epigenetic landscapes of each sex.
... Regarding PD, the loss of dopaminergic neurons in patients with it is thought to result from a combination of genetic and environmental factors. Previous findings suggest that changes in histone methylation may control substantia nigra neurons in patients with PD [55]. Caused by mutations of the HTT gene, HD progression in its early stages is potentially caused by transcriptional dysregulation due to changes in histone methylation [56]. ...
Histone methyltransferases (HMTs) and histone demethylases (HDMs) are critical enzymes that regulate chromatin dynamics and gene expression through the addition and removal of methyl groups on histone proteins. HMTs, such as PRC2 and SETD2, are involved in the trimethylation of histone H3 at lysine 27 and lysine 36, influencing gene silencing and activation. Dysregulation of these enzymes often leads to abnormal gene expression and contributes to tumorigenesis. In contrast, HDMs including KDM7A and KDM2A reverse these methylation marks, and their dysfunction can drive disease progression. In cancer, the aberrant activity of specific HMTs and HDMs can lead to the silencing of tumor suppressor genes or the activation of oncogenes, facilitating tumor progression and resistance to therapy. Conversely, in neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), disruptions in histone methylation dynamics are associated with neuronal loss, altered gene expression, and disease progression. We aimed to comprehend the odd activity of HMTs and HDMs and how they contribute to disease pathogenesis, highlighting their potential as therapeutic targets. By advancing our understanding of these epigenetic regulators, this review provides new insights into their roles in cancer and neurodegenerative diseases, offering a foundation for future research.
Накопленные в научной литературе данные свидетельствуют о том, что болезнь Паркинсона иногда развивается после перенесенных инфекций, вызванных вирусами SARS-CoV-2, Западного Нила, Коксаки, Сент-Луиса, японского энцефалита В, гепатита В и С, гриппа А, ВИЧ, герпес-вирусами, флавивирусами. Нейроинвазивные вирусы Западного Нила и ВИЧ активируют экспрессию альфа-синуклеина, а вирусы гриппа А, SARS-CoV-2 и Коксаки В3 способствуют агрегации альфа-синуклеина, который обладает биофизическими характеристиками противовирусных пептидов и необходим для нейрональной экспрессии генов, стимулируемых интерфероном. Данные механизмы могут быть триггерами болезни Паркинсона, прогрессирование которой обусловлено вовлечением в процесс активированных под их влиянием ретроэлементов, стимулирующих интерфероновый ответ, экспрессию и агрегацию альфа-синуклеина в головном мозге. Идентифицировано непосредственное активирующее влияние описанных вирусных инфекций на ретроэлементы генома человека. Дополнительными факторами являются ассоциированные с болезнью Паркинсона старение и полиморфизмы, расположенные в межгенных, интронных и регуляторных областях, где локализуются последовательности транспозонов. Кроме того, определено влияние особенностей распределения ретроэлементов в геномах популяций людей на предрасположенность к болезни Паркинсона и роль транспозонов в моногенных формах заболевания. Эффектами патологически активированных при болезни Паркинсона ретроэлементов являются изменения экспрессии произошедших от них микроРНК, которые способствуют нарушению эпигенетической регуляции генов в головном мозге и прогрессированию патологии. Анализ научной литературы позволил описать снижение уровня 15 таких микроРНК, которые могут служить инструментами для таргетной терапии заболевания.
Data accumulated in scientific literature indicate that Parkinson’s disease develops after infections caused by SARS-CoV-2, West Nile, Coxsackie, St. Louis viruses, Japanese encephalitis B, hepatitis B and C, influenza A, HIV, herpes viruses, flaviviruses. Neuroinvasive West Nile viruses and HIV activate expression of alpha-synuclein. Influenza A, SARS-CoV-2, and Coxsackie B3 viruses promote aggregation of alpha-synuclein, which has the biophysical characteristics of antiviral peptides and is required for neuronal interferon-stimulated gene expression. These mechanisms can be triggers of Parkinson’s disease, which progression is due to involvement of retroelements activated under their influence, stimulating the interferon response, expression and aggregation of alpha-synuclein in the brain. Direct activation of retroelements of the human genome by the described viral infections has been identified. Additional factors are aging and Parkinson’s disease-associated polymorphisms located in intergenic, intronic and regulatory regions where transposon sequences are localized. In addition, the influence of the distribution of retroelements in the genomes of human populations on susceptibility to Parkinson’s disease and the role of transposons in monogenic forms of the disease were determined. The effects of pathologically activated retroelements in Parkinson’s disease are changes in expression of microRNAs derived from them, which contribute to disruption of epigenetic regulation of genes in the brain and pathology progression. An analysis of the scientific literature made it possible to describe a decrease in the levels of 15 such microRNAs, which can serve as tools for targeted therapy of the disease.
