Interpretation and reflections on the prokineticin system is downregulated in idiopathic rapid eye movement sleep behavior disorder

Dear Editor, We read with great interest the recent article by Grillo et al. in SLEEP examining the prokineticin signaling pathway in idiopathic REM sleep behavior disorder (iRBD) [1]. iRBD is established as one of the most specific prodromal markers of α-synucleinopathy, with ˃90 per cent of patients progressing to Parkinson’s disease, dementia with Lewy bodies, or a related disorder within ~10 years [2]. Thus, identifying early molecular changes in iRBD is of clear importance. Grillo et al. used an innovative noninvasive approach to collect olfactory neurons (ONs) by nasal brushing, validating this easily obtained tissue as an accessible biomarker source. The authors then measured PROK2 protein (by immunofluorescence and Western blot), its receptors PKR1/PKR2 (by Reverse Transcription-Polymerase Chain Reaction (RT-PCR)), and oligomeric α-synuclein in ONs (and in a blood subset) of 28 polysomnography (PSG)-confirmed iRBD patients versus 28 controls. Notably, the cohort was well characterized clinically and all iRBD diagnoses were confirmed by polysomnography, which adds robustness to the findings.