Nuclear and Mitochondrial Genome, Epigenome and Gut Microbiome: Emerging Molecular Biomarkers for Parkinson's Disease

Abstract

Background: Parkinson's disease (PD) is currently the second most common neurodegenerative disorder, burdening about 10 million elderly individuals worldwide. The multifactorial nature of PD poses a difficult obstacle for understanding the mechanisms involved in its onset and progression. Currently, diagnosis depends on the appearance of clinical signs, some of which are shared among various neurologic disorders, hindering early diagnosis. There are no effective tools to prevent PD onset, detect the disease in early stages or accurately report the risk of disease progression. Hence, there is an increasing demand for biomarkers that may identify disease onset and progression, as treatment-based medicine may not be the best approach for PD. Over the last few decades, the search for molecular markers to predict susceptibility, aid in accurate diagnosis and evaluate the progress of PD have intensified, but strategies aimed to improve individualized patient care have not yet been established.

Conclusions: Genomic variation, regulation by epigenomic mechanisms, as well as the influence of the host gut microbiome seem to have a crucial role in the onset and progress of PD, thus are considered potential biomarkers. As such, the human nuclear and mitochondrial genome, epigenome, and the host gut microbiome might be the key elements to the rise of personalized medicine for PD patients.

Keywords: Parkinson’s disease; biomarkers; epigenetics; genetics; microbiome; mitochondria; neurodegeneration; non-coding RNAs; precision medicine.

Figure 1

Molecular factors that may be involved in Parkinson’s Disease onset and progression. There are various points of view in PD biomarker research, thus, there is a lot to be understood from the earliest molecular alterations until de development of the firsts symptoms. In this review, we decided to discuss these multi-omics factors to highlight how they can be applied for preventive measures.

Figure 2

Mechanisms of gene expression regulation. Gene expression is regulated by a network which includes chromatin modulators, with the addition of molecules such as acetyl and/or methyl in histones and the methylation of DNA strands. Additionally, ncRNAs participated in several steps both in transcriptional and post-transcriptional levels. Within the nucleus, ncRNAs may play the role of enhancers, transcription factors or as gene silencing tools. In cytoplasm, they may inhibit RNA translation or modulate the action of other ncRNAs and be used as a sponge of RBP, inducing mRNA degradation.