Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease

Li, Yan; Gu, Zhifeng; Lin, Shu-xian; Chen, Lei; Dzreyan, Valentina; Eid, Moez; Demyanenko, Svetlana; He, Bin

doi:10.20944/preprints202205.0158.v1

2022

DOI: 10.20944/preprints202205.0158.v1

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Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease

Yan Li¹,

Zhifeng Gu²,

Shu-xian Lin³

et al.

Abstract: Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that increasingly become a global threat for the elder people's health and life. Although there are some drugs in clinic for treating PD, these treatments only can alleviate the symptoms of PD patients but fail in curative therapies. Therefore, seeking other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable. In the last two decades, histone deacetylases as an … Show more

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2024

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Cited by 4 publications

References 136 publications

(202 reference statements)

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Unraveling the Epigenetic Landscape: Insights into Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis

Di Martino,

Marcozzi,

Bibbò

et al. 2024

Brain Sciences

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Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are examples of neurodegenerative movement disorders (NMDs), which are defined by a gradual loss of motor function that is frequently accompanied by cognitive decline. Although genetic abnormalities have long been acknowledged as significant factors, new research indicates that epigenetic alterations are crucial for the initiation and development of disease. This review delves into the complex interactions that exist between the pathophysiology of NMDs and epigenetic mechanisms such DNA methylation, histone modifications, and non-coding RNAs. Here, we examine how these epigenetic changes could affect protein aggregation, neuroinflammation, and gene expression patterns, thereby influencing the viability and functionality of neurons. Through the clarification of the epigenetic terrain underpinning neurodegenerative movement disorders, this review seeks to enhance comprehension of the underlying mechanisms of the illness and augment the creation of innovative therapeutic strategies.

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Unraveling the Epigenetic Landscape: Insights into Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis

Di Martino,

Marcozzi,

Bibbò

et al. 2024

Brain Sciences

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A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease

Tirozzi

Quiccione

Cerletti

et al. 2023

Cells

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Among candidate neurodegenerative/neuropsychiatric risk-predictive biomarkers, platelet count, mean platelet volume and platelet distribution width have been associated with the risk of major depressive disorder (MDD), Alzheimer’s disease (AD) and Parkinson’s disease (PD) through epidemiological and genomic studies, suggesting partial co-heritability. We exploited these relationships for a multi-trait association analysis, using publicly available summary statistics of genome-wide association studies (GWASs) of all traits reported above. Gene-based enrichment tests were carried out, as well as a network analysis of significantly enriched genes. We analyzed 4,540,326 single nucleotide polymorphisms shared among the analyzed GWASs, observing 149 genome-wide significant multi-trait LD-independent associations (p < 5 × 10−8) for AD, 70 for PD and 139 for MDD. Among these, 27 novel associations were detected for AD, 34 for PD and 40 for MDD. Out of 18,781 genes with annotated variants within ±10 kb, 62 genes were enriched for associations with AD, 70 with PD and 125 with MDD (p < 2.7 × 10−6). Of these, seven genes were novel susceptibility loci for AD (EPPK1, TTLL1, PACSIN2, TPM4, PIF1, ZNF689, AZGP1P1), two for PD (SLC26A1, EFNA3) and two for MDD (HSPH1, TRMT61A). The resulting network showed a significant excess of interactions (enrichment p = 1.0 × 10−16). The novel genes that were identified are involved in the organization of cytoskeletal architecture (EPPK1, TTLL1, PACSIN2, TPM4), telomere shortening (PIF1), the regulation of cellular aging (ZNF689, AZGP1P1) and neurodevelopment (EFNA3), thus, providing novel insights into the shared underlying biology of brain disorders and platelet parameters.

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The Role of the Gut Microbiota in Individuals with Irritable Bowel Syndrome: A Scoping Review

Nagamine

2024

Medicina

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Irritable bowel syndrome (IBS) represents the most prevalent disorder of brain–gut interaction, affecting approximately 10% of the global population. The objective of this study was to examine the mechanisms by which the gut microbiota contributes to the development of IBS. To this end, a review of articles that examined the gut microbiota of IBS patients was conducted. A search was conducted using PubMed and J-STAGE for articles published over the past five years that relate to the gut microbiota in patients with IBS. Individuals diagnosed with IBS display a reduction in alpha diversity and a decline in butyrate-producing bacteria, which collectively indicate a state of dysbiosis within their gut microbiota. Butyrate plays a dual role in the body, acting as a source of nutrition for the intestinal epithelium while also regulating the expression of dopamine transporters and D2 receptors in the central nervous system through epigenetic mechanisms. These characteristics may be linked to dysfunction of the central dopamine D2 pathway and play a role in the formation of various symptoms in IBS.

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Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease

Cited by 4 publications

References 136 publications

Unraveling the Epigenetic Landscape: Insights into Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis

Unraveling the Epigenetic Landscape: Insights into Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis

A Multi-Trait Association Analysis of Brain Disorders and Platelet Traits Identifies Novel Susceptibility Loci for Major Depression, Alzheimer’s and Parkinson’s Disease

The Role of the Gut Microbiota in Individuals with Irritable Bowel Syndrome: A Scoping Review

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