Abstract
Parkinson's Disease (PD) is a progressive neurodegenerative disorder affecting 2% of the population over 60 years old, yet the exact molecular mechanism underlying its pathogenesis remains elusive. PD is a multifactorial disease with genetic and environmental factors intricately associated. Recently, epigenetic mechanisms have been recognized as potential mediators of environmental factors participating in the pathogenesis of PD. Epigenetics refer to the heritable changes in gene expression that do not involve changes to the underlying DNA sequence. Altered epigenetic mechanisms have been attributed to PD, Alzheimer’s and Huntington’s disease. Several studies have shown that DNA methylation, histone modifications and non-coding RNAs mechanisms contribute to the pathogenesis of PD. Accumulation of toxic metals such as manganese and iron, due to abnormal environmental exposure or increased dietary intake, can impact varied components of the epigenetic machinery through free radical formation. Current pharmacological agents only provide symptomatic relief, of which levodopa still remains the gold standard. However, drugs that halt or delay progression of PD are still lacking. In recent years, there has been considerable progress in the development of epigenetic drugs as a novel therapeutic modality in the management of PD. Cell replacement therapy is a promising avenue for the treatment of PD with scientific research making great progress in the development of Induced Pluripotent Stem Cells (iPSCs) to produce midbrain dopamine phenotypes. With direct access to the neurons that are affected in PD, the pace of discovery should speed up and the cure for PD should become an attainable goal.
Highlights
Parkinson's Disease (PD) is a progressive neurodegenerative disorder affecting 2% of the population over 60 years old, yet the exact molecular mechanism underlying its pathogenesis remains elusive
We are recognizing that epigenetic mechanisms are at the forefront in manipulating complex biological processes, yet we remain at the very surface in understanding the role which is played by such epigenetic variations in the pathophysiology of complex multifactorial diseases, as is the case with PD
We have benefitted from a better understanding of the pathways involved in dopaminergic neurodegeneration at a molecular level, thanks to the increasing number of published papers aimed at understanding the epigenetics of PD
Summary
The histopathological trait of PD is the presence of fibrillar aggregates known as Lewy Bodies (LBs), with α-synuclein as the primary constituent. It is primarily the deficit of dopamine cells in the Substantia Nigra Pars Compacta (SNpc) that is thought to be responsible for all the motor complications of the disease. This selectivity goes further, in that not all of the dopamine neurons of the SNpc are involved with the disease. The pattern of cell loss seen in PD is unique as it neither occurs in other neurodegenerative diseases, nor in the normal ageing process. The reason behind such circumstantial susceptibility of cells affected in PD remains unclear
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
