Epigenetic modifications in Parkinson's disease: A critical review

Parkinson's Disease (PD) is a progressive neurodegenerative disorder expected to increase by over 50% by 2030 due to increasing life expectancy. The disease's hallmarks include slow movement, tremors, and postural instability. Impaired protein processing is a major factor in the pathophysiology of PD, leading to the buildup of aberrant protein aggregates, particularly misfolded α-synuclein, also known as Lewy bodies. These Lewy bodies lead to inflammation and further death of dopaminergic neurons, leading to imbalances in excitatory and inhibitory neurotransmitters, causing excessive uncontrollable movements called dyskinesias. It was previously suggested that a complex interplay involving hereditary and environmental variables causes the specific death of neurons in PD; however, the exact mechanism of the association involving the two primary modifiers is yet unknown. An increasing amount of research points to the involvement of epigenetics in the onset and course of several neurological conditions, such as PD. DNA methylation, post-modifications of histones, and non-coding RNAs are the primary examples of epigenetic alterations, that is defined as alterations to the expression of genes and functioning without modifications in DNA sequence. Epigenetic modifications play a significant role in the development of PD, with genes such as Parkin, PTEN-induced kinase 1 (PINK1), DJ1, Leucine-Rich Repeat Kinase 2 (LRRK2), and alpha-synuclein associated with the disease. The aberrant epigenetic changes implicated in the pathophysiology of PD and their impact on the design of novel therapeutic approaches are the primary focus of this review.