Epigenetic Biomarkers for Parkinson’s Disease: From Diagnostics to Therapeutics

Jakubowski, Jennifer L.; Labrie, Viviane

doi:10.3233/jpd-160914

Cited by 48 publications

(51 citation statements)

References 101 publications

(98 reference statements)

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“…The field of epigenetics focuses not within the DNA or RNA sequence itself but within the molecules and structures associated with DNA and RNA, such as the methylation pattern of DNA or post‐translational modification of histones. This is exemplified in preliminary work showing that there are DNA methylation patterns that may be unique to PD …”

Section: Geneticsmentioning

confidence: 97%

Parkinson's Disease Biomarkers: Where Are We and Where Do We Go Next?

Chahine

Stern

2017

Movement Disord Clin Pract

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Background Objective measures of Parkinson's disease (PD) are needed for purposes of diagnosis and prognostication, as well as identification of those at risk of PD. In this qualitative review, we provide an overview of the current state of the field of PD biomarker development, delineate challenges, and discuss how the field is evolving. Methods A search of PubMed was conducted for articles pertaining to objective biomarkers for PD. Articles were selected based on relevance and methodology; where available, meta‐analyses, systematic reviews, and comprehensive qualitative review articles were preferentially referenced. Results There are several potential sources of objective PD biomarkers including biofluids, peripheral tissue, imaging, genetics, and technology based objective motor testing. Approaches to biomarker identification include the candidate biomarker approach and unbiased discovery methods, each of which has advantages and disadvantages. Several emerging techniques hold promise in each of these areas. Advances in technology and bioinformatics, and the increasing availability of biobanks, are expected to facilitate future PD biomarker development. Conclusions The field of objective biomarkers for PD has made great progress but much remains to be done in translating putative biomarkers into tools useful in the clinic and for research. Multimodal biomarker platforms have the potential to capitalize on the utility and strengths of individual biomarkers. Rigorous methodology and standards for replication of findings will be key to meaningful progress in the field.

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Section: Geneticsmentioning

confidence: 97%

Parkinson's Disease Biomarkers: Where Are We and Where Do We Go Next?

Chahine

Stern

2017

Movement Disord Clin Pract

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“…Although the hypomethylation of SNCA intron1 in the pathogenesis of PD remains controversial with both positive and negative outcomes, the DNA methylation of this region in regulation of α-SYN in PD pathogenesis provides some valuable insights into the complex deregulation of SNCA . It is also important to add since epigenetic mark like the DNA methylation status of a gene is considered as heritable and stable, effort has been made to consider using SNCA or some other PD-implicated gene’s methylation status in the peripheral tissues as a biomarker for PD (Jakubowski and Labrie, 2017). Although the hypothesis looks appealing but we must also acknowledge that DNA methylation pattern may vary across different tissues or cell types and that this association of SNCA intron1 methylation pattern with PD is not unanimous.…”

Section: Regulation Of α-Synuclein Expression and Parkinson’s Diseasementioning

confidence: 99%

Deregulation of α-synuclein in Parkinson’s disease: Insight from epigenetic structure and transcriptional regulation of SNCA

Guhathakurta

Bok

Evangelista

et al. 2017

Progress in Neurobiology

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Understanding regulation of α-synuclein has long been a central focus for Parkinson’s disease (PD) researchers. Accumulation of this protein in the Lewy body or neurites, mutations in the coding region of the gene and strong association of α-synuclein encoding gene multiplication (duplication/triplication) with familial form of PD have indicated the importance of this molecule in pathogenesis of the disease. Several years of research identified many potential faulty pathways associated with accumulation of α-synuclein inside dopaminergic neurons and its transmission to neighboring ones. Concurrently, an appreciable body of research is growing to understand the epigenetic and genetic deregulation of α-synuclein that might contribute to the disease pathology. Completion of the ENCODE (Encyclopedia of DNA Elements) project and recent advancement made in the epigenetic and trans factor mediated regulation of each gene, has tremendously accelerated the need to carefully understand the epigenetic structure of the gene (SNCA) encoding α-synuclein protein in order to decipher the regulation and contribution of α-synuclein to the pathogenesis of PD. We have also analyzed the detailed epigenetic structure of this gene with knowledge from ENCODE database, which may open new avenues in α-synuclein research. Interestingly, we have found that the gene contains several transcriptionally activate histone modifications and associated potential transcription factor binding sites in the non-coding areas that strongly suggest alternative regulatory pathways. Altogether this review will provide interesting insight of α-synuclein gene regulation from epigenetic, genetic and post-transcriptional perspectives and their potential implication in the PD pathogenesis.

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“…Indeed, these epigenomic signatures could serve as a unifying predictor of disease risk as a result of multiple adverse exposures. This is being exploited in various disease fields to identify, and to validate, DNA methylation and miRNA biomarkers of risk of asthma, cancer, osteoarthritis, age-related neurodegenerative diseases and many other conditions (DeVries & Vercelli 2015;Terry et al 2016;Jakubowski & Labrie 2017). One of the important challenges in this field is the heterogeneity of epigenetic marks in different cell types and tissues.…”

Section: Public Health Implicationsmentioning

confidence: 99%

Nutrition, epigenetics and health through life

Malcomson

Mathers

2017

Nutrition Bulletin

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Epigenetics describe heritable changes to the genome without changes to the DNA sequence itself. Epigenetic marks include DNA methylation and histone modifications, and epigenetic molecules include microRNAs. Epigenetic mechanisms modulate gene expression and so regulate many cellular processes such as cell proliferation and cell death. As a consequence, changes to the epigenome may have consequences for the function of cells, tissues and organs and may modify the risk of developing disease. Epigenetic marks and molecules change during development and also during ageing; as we age, global DNA methylation declines whilst some specific genes become hypermethylated. Unlike the genome (DNA sequence), the epigenome is not fixed and the constellation of epigenetic marks and molecules is influenced by environmental exposures, including diet. Therefore, epigenetics provides a mechanism though which nutrition modulates health and wellbeing throughout the life course and, importantly, a plausible mechanism for the long‐term effects of early life nutritional exposures. There is growing evidence of the specific nutrients and other food constituents that influence the epigenome but, to date, the molecular pathways through which nutritional exposures and status are transduced (received and recorded) remain to be elucidated. Epigenetic patterns are promising candidate diet‐related biomarkers of ageing and of disease risk and, therefore, may be useful as surrogate endpoints in nutritional epidemiology and in dietary intervention studies.

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Epigenetic Biomarkers for Parkinson’s Disease: From Diagnostics to Therapeutics

Cited by 48 publications

References 101 publications

Parkinson's Disease Biomarkers: Where Are We and Where Do We Go Next?

Parkinson's Disease Biomarkers: Where Are We and Where Do We Go Next?

Deregulation of α-synuclein in Parkinson’s disease: Insight from epigenetic structure and transcriptional regulation of SNCA

Nutrition, epigenetics and health through life

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