Orexin and Parkinson's disease: A protective neuropeptide with therapeutic potential

Parkinson's disease (PD) is the second most common neurodegenerative disease caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. PD is characterized by motor dysfunctions as well as non-motor disorders. Orexin (also known as hypocretin) is a kind of neuropeptide involved in the regulation of motor control, the sleep/wake cycle, learning and memory, gastric motility and respiratory function. Several lines of evidence suggest that the orexinergic system is involved in the manifestations of PD, especially the non-motor disorders. Recent studies have revealed the protective actions and potential therapeutic applications of orexin in both cellular and animal models of PD. Here we present a brief overview of the involvement of the orexinergic system in PD, including the pathological changes in the lateral hypothalamus, the loss of orexinergic neurons and the fluctuation of orexin levels in CSF. Furthermore, we also review the neuroprotective effects of orexin in cellular and animal models of PD.