Abstract
Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data.
Highlights
Parkinsonian disorders are considered the second most common neurological diseases in humans [1]
The Long non-coding RNAs (lncRNAs) HOTAIR promotes the Parkinson’s disease (PD) phenotype induced by MPTP in mice and MPP in SH-SY5Y cells by upregulating the leucine-rich repeat kinase 2 LRRK2, an enzyme involved in PD development [124]
A study in a PD mouse model showed that when the lncRNA HOTAIR was knocked-down, this led to a reduction in the number of α-synuclein positive cells, and apoptosis of dopaminergic neurons [135]
Summary
Parkinsonian disorders are considered the second most common neurological diseases in humans [1]. The most recognizable symptom of the disease is the presence of tremors, the disease could be manifested with bradykinesia and other non-motor symptoms such as the accumulation of an aberrant form of alpha-synuclein or the mitochondrial dysfunction [3] This symptomatology arises after the loss of dopaminergic neurons in specific areas of the brain, like the motor cortex, the substantia nigra, and the thalamus. New biomarkers may help both to diagnose, risk stratify, and prognosticate PD patients at an early stage of the disease. Due to their presence and relative stability in the bloodstream—often packed in extracellular vesicles or exosomes—non-coding RNAs appeared as potential disease markers [19]. This review article presents an overview of the knowledge of the role of non-coding RNAs in PD, focusing on the interactions between the brain and the heart
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