Possible Roles of Epigenetics in Stem Cell Therapy for Parkinson’s Disease

Abstract

<jats:p> Parkinson’s disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons. PD has genetic and epigenetic influences that determine specific changes in the brain. Epigenetic changes result in defective methylation of genes leading to differential gene-expression causing PD. This review provides an overview of stem cell transplantations as potential therapies for PD, with a focus on the epigenetic changes, prior or following transplantation. To date, no reports have addressed epigenetic alterations following stem cell transplantation into the PD brain. Given the potential for affecting the efficacy of stem cell therapy, increased attention needs to be given to the epigenetic processes that occur during stem cell culture and transplantation to maximize the therapeutic potential of stem cells to PD. </jats:p>

Long Non-coding RNAs in Pathogenesis of Neurodegenerative Diseases

“…Caused by a variety of factors inside / outside of organisms, such as hormones, metabolism, diet, temperature, light, drugs, air pollution, age and so on, epigenetic changes could alter growth, development, reproduction and aging, and even contribute to pathogenesis of diseases such as neurological disorders. Significant efforts have been made in study of the epigenetic basis of neurodegenerative diseases (Thompson et al, 2020), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and so on.…”

“…Epigenetic modifications could be classified into three main categories including DNA modifications, histone modifications, and non-coding RNAs (ncRNAs)-mediated modifications (Hwang et al, 2017;Thompson et al, 2020). Of the DNA methylation modifications, 5methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), and N 6 -methyladenosine (m6A) have been identified and characterized as important epigenetic markers involved in regulation of gene expression in complicated mechanisms (Dermentzaki and Lotti, 2020;Pizzorusso and Tognini, 2020).…”

Stem Cell Transplantation for Parkinson’s Disease: Current Challenges and Perspectives

“…Genetic and epigenetic changes that occur when stem cells are cultured in vitro and passaged prior to transplantation can affect the therapeutic efficiency of these cells following transplantation. The loss of expression of specific genes during in vitro cell culturing causes problems relating to whether and when transplanted stem cells can differentiate into dopaminergic neurons in vivo [ 51 ]. For example, in a study, iPSCs were transplanted into the putamen of MPTP-treated PD monkeys, which were then divided into two groups on the basis of whether they had excellent or poor TH+ cell innervation; the PD monkeys that had excellent innervation exhibited the upregulation of 11 specific genes, among which the most prominent was Dlk1, a gene that has a role in facilitating the migration of dopaminergic neurons in the midbrain.…”

Molecular mechanisms of aging and anti-aging strategies

“…Conversely, enhanced mitochondrial function is accompanied by enhanced stem cell function and tissue regeneration [178]. Epigenetic regulation also plays an important role in the regulation of stem cell function and changes in the epigenome during aging affect the aging process of stem cells [179,180]. DNA methyltransferases balance self-renewal and differentiation in multiple adult stem cell compartments [181].…”