Epigenetics in Parkinson’s Disease

Abstract

Parkinson's disease (PD) is a highly complex neurodegenerative disorder with a multifactorial origin. Although several cellular mechanisms and genes have been implicated in the onset and progression of the disease, the precise molecular underpinnings of the disease remain unclear. In this context, epigenetic modulation of gene expression by environmental factors is emerging as an important mechanism in PD and in other neurodegenerative disorders. Thus, epigenetic mechanisms, such as DNA methylation, histone modifications and altered microRNA expression, have been under intense investigation due to their possible involvement in PD. Epigenetic modulation is responsible for inducing differential gene expression, a phenomenon which is essential throughout life in order to regulate multiple cellular responses such as development, cellular fate commitment and adaptation to the environment. Disturbances of a balanced gene expression can, therefore, have detrimental effects. Environmental factors can challenge the establishment and maintenance of epigenetic modifications and could thereby fill the gap in our further understanding of origin and/or progression of neurodegenerative diseases. In this chapter, we focus on the role of epigenetics in PD.

DNA methylation changes associated with Parkinson’s disease progression: outcomes from the first longitudinal genome-wide methylation analysis in blood

“…Epigenetic mechanisms are emerging as important factors in the molecular aetiology of neurodegenerative diseases, including PD [9,10]. Hypomethylation of the α-synuclein gene (SNCA) promotor region has been reported in substantia nigra of PD patients [11,12].…”

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

“…Recently, in particular for neurodegenerative disorders, the new field of mitoepigenetics is grabbing a growing attention [ 6 , 40 , 42 , 105 ]. The role of epigenetic modifications in neurodegeneration has been widely discussed and recognized [ 106 , 107 , 108 , 109 , 110 ] both in animal models and humans [ 108 , 111 , 112 , 113 , 114 ], in particular in the case of early-life exposure to xenobiotics [ 110 , 115 , 116 ]. Nuclear epigenetics can drive the expression of genes involved in mitochondrial homeostasis, and, conversely, metabolic alterations occurring in mitochondria may affect the availability of substrates for epigenetic enzymes [ 117 ], thus leading to alterations of epigenetic signatures in the nuclear genome [ 13 , 117 ].…”

Minimotifs dysfunction is pervasive in neurodegenerative disorders

“…Minimotifs are the foundation of the histone code. Enzymes that covalently modify minimotifs, including those in histones, are central to AD, PD, ALS, HD, and other polyQ track expansion disorders summarized in recent reviews [258][259][260][261][262][263].…”