Biological Function Analysis of MicroRNAs and Proteins in the Cerebrospinal Fluid of Patients with Parkinson's Disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by alpha-synuclein aggregation into Lewy bodies in the neurons. Cerebrospinal fluid (CSF) is considered the most suited source for investigating PD pathogenesis and identifying biomarkers. While microRNA (miRNA) profiling can aid in the investigation of post-transcriptional regulation in neurodegenerative diseases, information on miRNAs in the CSF of patients with PD remains limited. This review combines miRNA analysis with proteomic profiling to explore the collective impact of CSF miRNAs on the neurodegenerative mechanisms in PD. We constructed separate networks for altered miRNAs and proteomes using a bioinformatics method. Altered miRNAs were poorly linked to biological functions owing to limited information; however, changes in protein expression were strongly associated with biological functions. Subsequently, the networks were integrated for further analysis. In silico prediction from the integrated network revealed relationships between miRNAs and proteins, highlighting increased reactive oxygen species generation, neuronal loss, and neurodegeneration and suppressed ATP synthesis, mitochondrial function, and neurotransmitter release in PD. The approach suggests the potential of miRNAs as biomarkers for critical mechanisms underlying PD. The combined strategy could enhance our understanding of the complex biochemical networks of miRNAs in PD and support the development of diagnostic and therapeutic strategies for precision medicine.

Keywords: Parkinson’s disease; cerebrospinal fluid; integrated omics; microRNA; proteomes.

Figure 1

Biological function- and disease-related miRNAomic network from ingenuity pathway analysis. (A) Network of miRNAs (associated with pathological functions in Parkinson’s disease) from the cerebrospinal fluid (CSF) of patients. (B) In silico prediction of the miRNAomic network based on alterations of the miRNAs from CSF. The color intensity reflects the confidence of the prediction.

Figure 2

Biological function- and disease-related proteomic network from ingenuity pathway analysis. (A) Network of proteins associated with the pathological functions in Parkinson’s disease in the cerebrospinal fluid (CSF) of patients. (B) In silico prediction of the proteomic network based on the alterations of proteins from CSF. The color intensity reflects the confidence of the prediction.

Figure 3

Integrated omics network analysis and prediction from ingenuity pathway analysis. (A) Integrated network of the miRNAome and proteome. (B) In silico prediction of integrated network based on alterations of miRNAs and proteins. (C,D) Analyses of diseases and biological functions in upregulated molecules (C) and downregulated molecules (D) from the integrated omics dataset. A positive activation z-score indicates the activation of the function. The color intensity reflects the confidence of the prediction.