Potential of Non-Coding RNA as Biomarkers for Progressive Supranuclear Palsy

Abstract

Objective markers for the neurodegenerative disorder progressive supranuclear palsy (PSP) are needed to provide a timely diagnosis with greater certainty. Non-coding RNA (ncRNA), including microRNA, piwi-interacting RNA, and transfer RNA, are good candidate markers in other neurodegenerative diseases, but have not been investigated in PSP. Therefore, as proof of principle, we sought to identify whether they were dysregulated in matched serum and cerebrospinal fluid (CSF) samples of patients with PSP. Small RNA-seq was undertaken on serum and CSF samples from healthy controls (n = 20) and patients with PSP (n = 31) in two cohorts, with reverse transcription-quantitative PCR (RT-qPCR) to confirm their dysregulation. Using RT-qPCR, we found in serum significant down-regulation in hsa-miR-92a-3p, hsa-miR-626, hsa-piR-31068, and tRNA-ValCAC. In CSF, both hsa-let-7a-5p and hsa-piR-31068 showed significant up-regulation, consistent with their changes observed in the RNA-seq results. Interestingly, we saw no correlation in the expression of hsa-piR-31068 within our matched serum and CSF samples, suggesting there is no common dysregulatory mechanism between the two biofluids. While these changes were in a small cohort of samples, we have provided novel evidence that ncRNA in biofluids could be possible diagnostic biomarkers for PSP and further work will help to expand this potential.

Small non-coding RNA content in plasma-derived extracellular vesicles distinguish ataxic SCA3 mutation carriers from pre-ataxic and control subjects

“…More recently, other classes of RNAs, namely tRNAs, piRNAs, snoRNAs, and mtRNAs, were also shown to be dysregulated in the context of neurodegenerative diseases [52][53][54][55]. tRNAs and piRNAs revealed to be the second and third most abundant RNA biotypes in EVs across all groups, respectively.…”

tRNA fragment biomarkers of Neurological Disease: Challenges and Opportunities

“…Patients with PSP can exhibit a range of cognitive and motor symptoms including supranuclear gaze palsy, which gave the disorder its name, but can also exhibit Parkinsonism features including posturing and rigidity which can lead to difficulty in diagnosis. Simoes et al, performed small non-coding RNA sequencing on matched serum and CSF samples from patients diagnosed with possible or probable PSP and healthy controls 78 . They identified 16 dysregulated tRFs in serum including tRFs derived from GlyGCC and GluCTC but read counts for tRFs were low in serum and only ValCAC tRF downregulation was confirmed by qPCR.…”