Effects of Ghrelin Hormone on Alzheimer's and Parkinson's Disease: A Systematic Review of the Existing Literature.

Ghrelin is an orexigenic hormone secreted mainly in the stomach and small intestine. It has many functions, including appetite stimulation, growth hormone release triggering, and maintaining glucose and energy homeostasis. It has also been linked to many neuroregenerative and neuroprotective activities via its activity on the growth hormone secretagogue receptor 1a (GHS-R1a). In brain tissues, it has been revealed that only the acylated ghrelin (AG) but not the unacylated ghrelin (UAG) has the affinity to GHS-R1a. In addition, AG has been shown to undergo fast enzymatic conversion into the inactive UAG form in the serum. Many experimental trials were conducted to study ghrelin's effect on Alzheimer's disease (AD) and Parkinson's disease (PD), but there have not been systematic reviews made to date. This systematic review highlighted the findings from preclinical trials between 2010 and July 2023, in which ghrelin and/or one of its agonists have been investigated for their effects in treating AD and PD. The search databases used were Embase, Cochrane, and Medline. All articles reviewed were animal studies as there were no clinical trials. The findings on AD showed that AG has demonstrated improved outcomes histopathologically and symptomatically. Meanwhile for PD, AG was found to have neuroprotective effects, especially in the early stage of the disease. This systematic review paves the way for more studies to be done to ensure the applicability of ghrelin and/or its agonists in treating and/or slowing the progression of AD, and early prevention and diagnosis of PD.