Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson's patients.

Autor:	Aguilar MA; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.; Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United States., Ebanks S; Department of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States., Markus H; Department of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States., Lewis MM; Department of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States.; Department of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States., Midya V; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States., Vrana K; Department of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States., Huang X; Department of Neurology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States.; Department of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States., Hall MA; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.; Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United States., Kawasawa YI; Department of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, United States.; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, United States.; Institute for Personalized Medicine, College of Medicine, The Pennsylvania State University, Hershey, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2023 Jul 06; Vol. 17, pp. 1145923. Date of Electronic Publication: 2023 Jul 06 (Print Publication: 2023).
DOI:	10.3389/fnins.2023.1145923
Abstrakt:	Background: Circulating small RNAs (smRNAs) originate from diverse tissues and organs. Previous studies investigating smRNAs as potential biomarkers for Parkinson's disease (PD) have yielded inconsistent results. We investigated whether smRNA profiles from neuronally-enriched serum exosomes and microvesicles are altered in PD patients and discriminate PD subjects from controls. Methods: Demographic, clinical, and serum samples were obtained from 60 PD subjects and 40 age- and sex-matched controls. Exosomes and microvesicles were extracted and isolated using a validated neuronal membrane marker (CD171). Sequencing and bioinformatics analyses were used to identify differentially expressed smRNAs in PD and control samples. SmRNAs also were tested for association with clinical metrics. Logistic regression and random forest classification models evaluated the discriminative value of the smRNAs. Results: In serum CD171 enriched exosomes and microvesicles, a panel of 29 smRNAs was expressed differentially between PD and controls (false discovery rate (FDR) < 0.05). Among the smRNAs, 23 were upregulated and 6 were downregulated in PD patients. Pathway analysis revealed links to cellular proliferation regulation and signaling. Least absolute shrinkage and selection operator adjusted for the multicollinearity of these smRNAs and association tests to clinical parameters via linear regression did not yield significant results. Univariate logistic regression models showed that four smRNAs achieved an AUC ≥ 0.74 to discriminate PD subjects from controls. The random forest model had an AUC of 0.942 for the 29 smRNA panel. Conclusion: CD171-enriched exosomes and microvesicles contain the differential expression of smRNAs between PD and controls. Future studies are warranted to follow up on the findings and understand the scientific and clinical relevance. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Aguilar, Ebanks, Markus, Lewis, Midya, Vrana, Huang, Hall and Kawasawa.)
Databáze:	MEDLINE
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