The role of orexin in Parkinson's disease

Abstract Emerging evidence has implicated the orexin system in non‐motor pathogenesis of Parkinson's disease. It has also been suggested the orexin system is involved in the modulation of motor control, further implicating the orexin system in Parkinson's disease. Parkinson's disease is the second most common neurodegenerative disease with millions of people suffering worldwide with motor and non‐motor symptoms, significantly affecting their quality of life. Treatments are based solely on symptomatic management and no cure currently exists. The orexin system has the potential to be a treatment target in Parkinson's disease, particularly in the non‐motor stage. In this review, the most current evidence on the orexin system in Parkinson's disease and its potential role in motor and non‐motor symptoms of the disease is summarized. This review begins with a brief overview of Parkinson's disease, animal models of the disease, and the orexin system. This leads into discussion of the possible roles of orexin neurons in Parkinson's disease and levels of orexin in the cerebral spinal fluid and plasma in Parkinson's disease and animal models of the disease. The role of orexin is then discussed in relation to symptoms of the disease including motor control, sleep, cognitive impairment, psychological behaviors, and the gastrointestinal system. The neuroprotective effects of orexin are also summarized in preclinical models of the disease.