Dataset Information

Epigenetic Biomarkers for Parkinson's Disease: From Diagnostics to Therapeutics.

ABSTRACT: Parkinson's disease (PD) is a prevalent neurodegenerative illness that is often diagnosed after significant pathology and neuronal cell loss has occurred. Biomarkers of PD are greatly needed for early diagnosis, as well as for the prediction of disease progression and treatment outcome. In this regard, the epigenome, which is partially dynamic, holds considerable promise for the development of molecular biomarkers for PD. Epigenetic marks are modified by both DNA sequence and environmental factors associated with PD, and such marks could serve as a unifying predictor of at-risk individuals. Epigenetic abnormalities have been detected in PD and other age-dependent neurodegenerative diseases, some of which were reported to occur early on and were reversible by PD medications. Emerging reports indicate that certain epigenetic differences observed in the PD brain are detectable in more easily accessible tissues. In this review, we examine epigenetic-based strategies for the development of PD biomarkers. Despite the complexities and challenges faced, the epigenome offers a new source of biomarkers with potential etiological relevance to PD, and may expand opportunities for personalized therapies.

SUBMITTER: Jakubowski JL

PROVIDER: S-EPMC5302044 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Epigenetic Biomarkers for Parkinson's Disease: From Diagnostics to Therapeutics.

Jakubowski Jennifer L JL Labrie Viviane V

Journal of Parkinson's disease 20170101 1

Parkinson's disease (PD) is a prevalent neurodegenerative illness that is often diagnosed after significant pathology and neuronal cell loss has occurred. Biomarkers of PD are greatly needed for early diagnosis, as well as for the prediction of disease progression and treatment outcome. In this regard, the epigenome, which is partially dynamic, holds considerable promise for the development of molecular biomarkers for PD. Epigenetic marks are modified by both DNA sequence and environmental facto ...[more]

PMID: 27792016

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Project description:Parkinson's disease (PD) is a progressive neurodegenerative disorder that is diagnosed largely on clinical grounds due to characteristic motor manifestations that result from the loss of nigrostriatal dopaminergic neurons. While traditional pharmacological approaches to enhance dopamine levels, such as with L-dopa, can be very effective initially, the chronic use of this dopamine precursor is commonly plagued with motor response complications. Additionally, with advancing disease, non-motor manifestations emerge, including psychosis and dementia that compound patient disability. The pathology includes hallmark intraneuronal inclusions known as Lewy bodies and Lewy neurites that contain fibrillar α-synuclein aggregates. Evidence has also accumulated that these aggregates can propagate across synaptically connected brain regions, a phenomenon that can explain the progressive nature of the disease and the emergence of additional symptoms over time. The level of α-synuclein is believed to play a critical role in its fibrillization and aggregation. Accordingly, nucleic acid-based therapeutics for PD include strategies to deliver dopamine biosynthetic enzymes to boost dopamine production or modulate the basal ganglia circuitry in order to improve motor symptoms. Delivery of trophic factors that might enhance the survival of dopamine neurons is another strategy that has been attempted. These gene therapy approaches utilize viral vectors and are delivered stereotaxically in the brain. Alternative disease-modifying strategies focus on downregulating the expression of the α-synuclein gene using various techniques, including modified antisense oligonucleotides, short hairpin RNA, short interfering RNA, and microRNA. The latter approaches also have implications for dementia with Lewy bodies. Other PD genes can also be targeted using nucleic acids. In this review, we detail these various strategies that are still experimental, and discuss the challenges and opportunities of nucleic acid-based therapeutics for PD.

Dataset Information

Epigenetic Biomarkers for Parkinson's Disease: From Diagnostics to Therapeutics.

Publications

Epigenetic Biomarkers for Parkinson's Disease: From Diagnostics to Therapeutics.

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