Exploring the role of Orexin-A neuropeptide in Parkinson's disease: A systematic review and meta-analysis

Abstract

BackgroundParkinson's disease (PD) is a progressive neurological condition that affects movement and coordination. Orexin-A (OXA) is an excitatory neuropeptide that is found throughout the central nervous system. There is growing interest in investigating the potential diagnostic and therapeutic utility of OXA in PD. To date, studies have reported a wide range of OXA concentrations in patients with PD. In this review, we discuss the current understanding of the dysregulation of OXA in PD and analyze its levels in the CSF. MethodsWe searched six databases (PubMed, Scopus, Web of Science, EMBASE, ProQuest, and EBSCOHost) and preprint servers using a predetermined search strategy through 4th March 4, 2023. The search keywords included “Parkinson’s disease”, “Orexin-A”, “Hypocretin-1”, “cerebrospinal fluid”, and “CSF”. Studies that reported OXA/Hypocretin-1 levels in the CSF of patients with PD were included. Two researchers independently reviewed the records and extracted data. FindingsEighteen studies involving 244 patients were analyzed. CSF Orexin-A concentrations were lower in patients with Parkinson’s disease than in controls, with a mean difference of −59.21 (95 % CI: −89.10 to −29.32). The mean OXA levels were 281.52 (95 % CI: 226.65–336.40). ConclusionOur analysis reveals lower concentrations of orexin-A in the cerebrospinal fluid of Parkinson's disease patients compared to controls, but within the normal range. These findings suggest a potential, but not significant, disruption in the orexinergic system associated with the disease.