Ghrelin is a circulating orexigenic signal that rises with prolonged fasting and falls postprandially. Ghrelin regulates energy homeostasis by stimulating appetite and body weight; however, it also has many nonmetabolic functions including enhanced learning and memory, anxiolytic effects as well as being neuroprotective. In Parkinson s disease, ghrelin enhances dopaminergic survival via reduced microglial and caspase activation and improved mitochondrial function. As mitochondrial dysfunction contributes to Parkinson s disease, any agent that enhances mitochondrial function could be a potential therapeutic target. We propose that ghrelin provides neuroprotective effects via AMPK (5 adenosine monophosphate-activated protein kinase) activation and enhanced mitophagy (removal of damaged mitochondria) to ultimately enhance mitochondrial bioenergetics. AMPK activation shifts energy balance from a negative to a neutral state and has a role in regulating mitochondrial biogenesis and reducing reactive oxygen species production. Mitophagy is important in Parkinson s disease because damaged mitochondria produce reactive oxygen species resulting in damage to intracellular proteins, lipids and DNA predisposing them to neurodegeneration. Many genetic mutations linked to Parkinson s disease are due to abnormal mitochondrial function and mitophagy, for example LRRK2, PINK1 and Parkin. An interaction between ghrelin and these classic Parkinson s disease markers has not been observed, however by enhancing mitochondrial function, ghrelin or AMPK is a potential therapeutic target for slowing the progression of Parkinson s disease symptoms, both motor and nonmotor.
|Pages (from-to)||25 - 36|
|Number of pages||12|
|Journal||Therapeutic Advances in Endocrinology and Metabolism|
|Publication status||Published - 2013|