Objective: We investigated the effects of discoidin domain receptor (DDR)-1 inhibition on CSF miRNAs in Parkinson’s disease patients.

Background: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, predominantlythrough silencing of target mRNA, although gene activation has also been reported
Objectives

Method: Cell-free total RNA was isolated from 200μl of CSF using the QiagenmiRNAeasy serum/plasma extraction kit (Qiagen, 217184). Quality control analysis to confirm RNA was performed on each sample using UV-VIS spectroscopy on a Nanodrop ND-1000 (ThermoFisher).

Results: We observed significant changes in the expression of microRNAs upstream of angiogenesis and autophagy pathways in placebo-treated patients, indicating impairment of brain vasculature and cellular transport in Parkinson’s progression. Interestingly, miRNAs associated with angiogenesis correlate with a decline in motor and non-motor symptoms in Parkinson’s patients. Furthermore, nilotinib, 300mg, a potent DDR1inhibitor, significantly reverses miRNA changes versus nilotinib, 150mg or placebo; and these changes correlate with long-term motor and non-motor stability.

Conclusion: Collectively, this study demonstrates vascular and autophagy defects in Parkinson’s disease progression and DDR1 inhibition reverses these effects and improves clinical outcomes. Our findings suggest that CSF miRNA may serve as a biomarker for drug response and that DDR1 inhibition alters biological mechanisms that positively affect brain pathology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/csf-microrna-analysis-reveals-angiogenesis-and-autophagy-defects-in-parkinsons-diseasepatients/