Pituitary Adenylate Cyclase-Activating Polypeptide: A Potent Therapeutic Agent in Oxidative Stress

Abstract

Stroke is a life-threatening condition that is characterized by secondary cell death processes that occur after the initial disruption of blood flow to the brain. The inability of endogenous repair mechanisms to sufficiently support functional recovery in stroke patients and the inadequate treatment options available are cause for concern. The pathology behind oxidative stress in stroke is of particular interest due to its detrimental effects on the brain. The oxidative stress caused by ischemic stroke overwhelms the neutralization capacity of the body’s endogenous antioxidant system, which leads to an overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and eventually results in cell death. The overproduction of ROS compromises the functional and structural integrity of brain tissue. Therefore, it is essential to investigate the mechanisms involved in oxidative stress to help obtain adequate treatment options for stroke. Here, we focus on the latest preclinical research that details the mechanisms behind secondary cell death processes that cause many central nervous system (CNS) disorders, as well as research that relates to how the neuroprotective molecular mechanisms of pituitary adenylate cyclase-activating polypeptides (PACAPs) could make these molecules an ideal candidate for the treatment of stroke.

Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract

“…Additionally, in long-term diabetes, insulin-growth factor I (IGF-I) is reduced, which leads to atrophic changes in smooth muscles, resulting in an impaired GIT function [ 37 ]. The antioxidative effect of PACAP has been identified in various culture studies in vitro and in various animal models in vivo [ 10 , 16 , 31 , 38 ]. Studies of PACAP-deficient mice have shown that endogenous PACAP plays a crucial role in reducing oxidative stress and its deficiency leads to severe oxidative damage [ 38 ].…”

“…The antioxidative effect of PACAP has been identified in various culture studies in vitro and in various animal models in vivo [ 10 , 16 , 31 , 38 ]. Studies of PACAP-deficient mice have shown that endogenous PACAP plays a crucial role in reducing oxidative stress and its deficiency leads to severe oxidative damage [ 38 ]. Kasica et al [ 39 ] showed that PACAP has an anti-apoptotic effect on zebrafish hair cells by reducing the cleaved caspase-3 level and reducing oxidative stress.…”

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Physiological and Pathological Processes within the Gastrointestinal Tract: A Review

“…The protective role of PACAP on intestinal epithelial cells having high turnover (INT 407) against oxidative stress was also demonstrated [104]. Recent research elucidated that PACAP preserves mitochondrial functionality and suppress apoptotic signaling in oxidative stress condition [105]. In turn, in atrophic rat ileum, decreased expression of PACAP was reported, as well as a transient supersensitivity of the longitudinal muscle to the PACAP [106].…”

“…An increasing number of reports have confirmed the involvement of PACAP in the regulation of pathological processes in the GI tract. PACAP has been shown to have anti-inflammatory, antioxidant and cytoprotective effects [7,[10][11][12][13][14][15][29][30][31][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109]. The involvement of PACAP in the regulation of gastrointestinal disorders is presented below and summarized in Table 2.…”

Shorebirds’ Longer Migratory Distances Are Associated With Larger ADCYAP1 Microsatellites and Greater Morphological Complexity of Hippocampal Astrocytes

“…In the periphery it causes increased insulin (Shao et al, 2013) and histamine (Schubert, 2003) secretions, controls vasodilation (Baliga et al, 2013), bronchodilation (Lindén et al, 1999;Kinhult et al, 2000), modulates innate and adaptive immunity (Ganea and Delgado, 2002), alters intestinal motility (Bornstein et al, 2004) and stimulates cellular proliferation as well as differentiation (Nowak and Zawilska, 2003;Vaudry et al, 2009;Prisco et al, 2019;Karpiesiuk and Palus, 2021). In the CNS, PACAP displays pleiotropic activity, including functions as a hypophysiotropic hormone (Vélez and Unniappan, 2020), neuromodulator, and neurotrophic factor (Sadanandan et al, 2021). PACAP is also involved in the rhythmicity of melatonin production and in the increase of cAMP in birds (Nakahara et al, 2002).…”