Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, being largely characterized by motor features. MicroRNAs (miRNAs) are small non-coding RNAs, whose deregulation has been associated with neurodegeneration in PD. In this study, miRNAs targeting cell death and/or inflammation pathways were selected and their expression compared in the serum of PD patients and healthy controls. We used two independent cohorts (discovery and validation) of 20 idiopathic PD patients (iPD) and 20 healthy controls each. We also analyzed an additional group of 45 patients with a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (LRRK2-PD). miRNA expression was determined using Taqman qRT-PCR and their performance to discriminate between groups was assessed by receiver operating characteristic (ROC) curve analysis. We found miR-146a, miR-335-3p, and miR-335-5p downregulated in iPD and LRRK2-PD patients versus controls in both cohorts. In addition, miR-155 was upregulated in LRRK2-PD compared to iPD patients showing an appropriate value of area under the ROC curve (AUC 0.80) to discriminate between the two groups. In conclusion, our study identified a panel of inflammatory related miRNAs differentially expressed between PD patients and healthy controls that highlight key pathophysiological processes and may contribute to improve disease diagnosis.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, affecting 1–2% of people older than 65 years
We investigated the profile of a selected set of inflammatory miRNAs, miR-21-5p, miR-34a-5p, miR-34b-5p, miR-34c-5p, miR-146a-5p, miR-155-5p, miR-335-3p, and miR-335-5p- in the serum of idiopathic PD patients and patients carrying a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (LRRK2-PD), and of age-matched healthy controls, and explored its value as molecular markers of disease pathogenesis
An additional group composed by 45 LRRK2-PD patients was studied and results compared with the groups of idiopathic PD patients (iPD) patients and healthy controls
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, affecting 1–2% of people older than 65 years. Around 10% of all cases are considered to be related to heritable forms of PD [1]. LRRK2 mutations account for 5–6% of familial PD, and for 1–2% of sporadic cases [2], due to incomplete penetrance. European Countries, such as Portugal and Spain, and even higher in Jewish and North African Arab populations, where mean frequencies are around 40% and 33% of familial and sporadic PD cases, respectively [3]. PD is clinically characterized by parkinsonism, with the presence of bradykinesia associated with rest tremor and/or rigidity, and associated with other motor and nonmotor symptoms, such as hyposmia and sleep disorders, and dysautonomic symptoms, such as constipation, postural hypotension, pain, fatigue, psychiatric problems, and impaired cognition [4,5]. Definite diagnosis is only possible post mortem by neuropathological studies, where neurodegeneration of dopaminergic cells of the substantia nigra pars compacta and the accumulation of neuronal cytoplasmatic inclusions known as Lewy bodies (LBs), composed of misfolded forms of α-synuclein (ASYN), are usually present [6]
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