Neuroprotective Effects of Brain-Gut Peptides: A Potential Therapy for Parkinson's Disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease and is typically associated with progressive motor and non-motor dysfunctions. Currently, dopamine replacement therapy is mainly used to relieve the motor symptoms, while its long-term application can lead to various complications and does not cure the disease. Numerous studies have demonstrated that many brain-gut peptides have neuroprotective effects in vivo and in vitro, and may be a promising treatment for PD. In recent years, some progress has been made in studies on the neuroprotective effects of some newly-discovered brain-gut peptides, such as glucagon-like peptide 1, pituitary adenylate cyclase activating polypeptide, nesfatin-1, and ghrelin. However, there is still no systematic review on the neuroprotective effects common to these peptides. Thus, here we review the neuroprotective effects and the associated mechanisms of these four peptides, as well as other brain-gut peptides related to PD, in the hope of providing new ideas for the treatment of PD and related clinical research.

Keywords: Ghrelin; Glucagon-like peptide 1; Nesfatin-1; Parkinson’s disease; Pituitary adenylate cyclase activating polypeptide.

Fig. 1

The neuroprotective effects of the brain-gut peptides GLP-1, PACAP, nesfatin-1, and ghrelin, as well as related signaling pathways. PAC1R, PAC1 receptor; VPAC1R, VPAC1 receptor; TLR4, Toll-like receptor 4; RAGE, receptor for advanced glycation end product; GHSR1a, growth hormone secretagogue receptor 1a; nesfatin-1R, nesfatin-1 receptor; PKC, protein kinase C; cAMP, cyclic AMP; PKA, protein kinase A; MEK, mitogen-activated protein kinase kinase; ERK, extracellular regulated protein kinase; PI3K, phosphoinositide 3-kinase; AKT, protein kinase B; Nrf2, nuclear factor erythroid 2-related factor 2; caspase 3, cysteinyl aspartate-cleaving protease 3; CREB, cAMP response element-binding protein; NFκB, nuclear factor-kappa B; Bcl2, B-cell lymphoma 2; GSK-3β, glycogen synthase kinase 3 beta; CaMK, CaM-dependent protein kinase; AMPK, AMP-activated protein kinase; ULK, Unc-51 like autophagy activating kinase; mTOR, mammalian target of rapamycin; SIRT, sirtuin; UCP2, uncoupling protein 2; ↓, activation; ┴, inhibition;┋, many steps omitted.