Alternative Routes of Administration of the Neuroprotective Pituitary Adenylate Cyclase Activating Polypeptide

Reglődi, Dóra; Atlasz, Tamás; Jungling, Adel; Szabó, Edina; Kovari, Petra; Manavalan, Sridharan; Tamás, Andrea

doi:10.2174/1381612824666181112110934

Cited by 13 publications

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“…The therapeutic value of PACAP and/or its derivatives has emerged in light of its strong neuroprotective and general cytoprotective properties as well as potent vasodilatory and several other biological effects (Cline et al 2019;Jozsa et al 2019;Parsons and May 2019;Reglodi et al 2018a;Shioda et al 2019;Van et al 2019;Vaudry et al 2009). PACAP has shown in vivo protective effects in animal models of cerebral ischemia, Parkinson's and Alzheimer's disease, Huntington chorea, traumatic brain and spinal cord injury, and different retinal pathologies (Reglodi et al 2017(Reglodi et al , 2018b.…”

Section: Discussionmentioning

confidence: 99%

“…Several other routes of administration have been proven to provide protective effects of PACAP in the nervous system and peripheral organs, such as intracerebral, intrathecal, intracerebroventricular, intravitreal and systemic treatments, as well as intravenous, intraperitoneal and subcutaneous administration. Other options include emerging therapeutic approaches such as intranasal and eye drop treatments (Cabezas-Llobet et al 2018;Meredith et al 2015;Reglodi et al 2018a). As far as protection in the eye is concerned, the intravitreal approach is the first choice for treatment in animal models of ocular diseases (Atlasz et al 2016;Kiss et al 2006;Reglodi et al 2018a).…”

Section: Discussionmentioning

confidence: 99%

“…Other options include emerging therapeutic approaches such as intranasal and eye drop treatments (Cabezas-Llobet et al 2018;Meredith et al 2015;Reglodi et al 2018a). As far as protection in the eye is concerned, the intravitreal approach is the first choice for treatment in animal models of ocular diseases (Atlasz et al 2016;Kiss et al 2006;Reglodi et al 2018a). This approach has led to the demonstration of the retinoprotective effects of PACAP in models of retinal hypoperfusion (Atlasz et al 2007), traumatic optic nerve injury (Seki et al 2008 Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) exists in two active forms, PACAP1-38 and PACAP1-27, both of which are well-established neuro-and general cytoprotective peptides, with 38 and 27 amino acid residues, respectively (Reglodi et al 2017(Reglodi et al , 2018aShioda and Nakamachi 2015). PACAP1-27 is the form with the shorter C-terminal, representing about 10% of the naturally occurring peptide (Miyata et al 1990;Vaudry et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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Stability Test of PACAP in Eye Drops

et al. 2020

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PACAP is a neuropeptide with widespread distribution and diverse biological functions. It has strong cytoprotective effects mediated mainly through specific PAC1 receptors. Experimental data show protective effects of PACAP in the retina and cornea in several pathological conditions. Although intravitreal injections are a common practice in some ocular diseases, delivery of therapeutic agents in the form of eye drops would be more convenient and would lead to fewer side effects. We have previously shown that PACAP, in the form of eye drops, is able to pass through the ocular barriers and can exert retinoprotective effects. As eye drops represent a promising form of administration of PACAP in ocular diseases, it is important to investigate the stability of PACAP in solutions used in eye drops. In this study, the stability of PACAP1-27 and PACAP1-38 in eye drops was measured in four common media and a commercially available artificial tear solution at both room temperature and +4°C. Mass spectrometry results show that the highest stability was gained with PACAP1-38 in water and 0.9% saline solution at +4°C, representing 80-90% drug persistence after 2 weeks. PACAP1-38 in the artificial tear showed very fast degradation at room temperature, but was stable at +4°C. In summary, PACAP1-38 has higher stability than PACAP1-27, with highest stability at +4°C in water solution, but both peptides in each medium can be stored for relatively longer periods without significant degradation. These data can provide reference for future therapeutic use of PACAP in eye drops.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stability Test of PACAP in Eye Drops

et al. 2020

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“…PACAP is now a well-known neuroprotective factor with strong effects in several in vitro and in vivo animal models [20,[22][23][24][25]. Among others, PACAP has potent neuroprotective effects in models of focal and global cerebral ischemia [23,25,26], retinal pathologies [27], neuronal toxicities [22], multiple sclerosis and other inflammatory conditions [28,29], as well as in models of neurodegenerative diseases like Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis [30][31][32][33]. Few studies indicate the potential protective effect of PACAP also in traumatic central and peripheral nervous system injuries, which have been summarized in an earlier review paper [34].…”

Section: General Overviewmentioning

confidence: 99%

The Neuroprotective and Biomarker Potential of PACAP in Human Traumatic Brain Injury

Tóth

Tamás

Reglődi

2020

IJMS

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Traumatic brain injury remains a growing public health concern and represents the greatest contributor to death and disability globally among all trauma-related injuries. There are limited clinical data regarding biomarkers in the diagnosis and outcome prediction of TBI. The lack of real effective treatment for recovery calls for research of TBI to be shifted into the area of prevention, treatment of secondary brain injury and neurorehabilitation. The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has been reported to act as a hormone, a neuromodulator, a neurotransmitter and a trophic factor, and has been implicated in a variety of developmental and regenerative processes. The importance of PACAP in neuronal regeneration lies in the upregulation of endogenous PACAP and its receptors and the protective effect of exogenous PACAP after different central nervous system injury. The aim of this minireview is to summarize both the therapeutic and biomarker potential of the neuropeptide PACAP, as a novel possible target molecule presently being investigated in several human conditions including TBI, and with encouraging results in animal models of TBI.

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Age-related alterations of articular cartilage in pituitary adenylate cyclase–activating polypeptide (PACAP) gene–deficient mice

et al. 2019

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Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionarly conserved neuropeptide which is produced by various neuronal and non-neuronal cells, including cartilage and bone cells. PACAP has trophic functions in tissue development, and it also plays a role in cellular and tissue aging. PACAP takes part in the regulation of chondrogenesis, which prevents insufficient cartilage formation caused by oxidative and mechanical stress. PACAP knockout (KO) mice have been shown to display early aging signs affecting several organs. In the present work, we investigated articular cartilage of knee joints in young and aged wild-type (WT) and PACAP KO mice. A significant increase in the thickness of articular cartilage was detected in aged PACAP gene–deficient mice. Amongst PACAP receptors, dominantly PAC1 receptor was expressed in WT knee joints and a remarkable decrease was found in aged PACAP KO mice. Expression of PKA-regulated transcription factors, Sox5, Sox9 and CREB, decreased both in young and aged gene deficient mice, while Sox6, collagen type II and aggrecan expressions were elevated in young but were reduced in aged PACAP KO animals. Increased expression of hyaluronan (HA) synthases and HA-binding proteins was detected parallel with an elevated presence of HA in aged PACAP KO mice. Expression of bone related collagens (I and X) was augmented in young and aged animals. These results suggest that loss of PACAP signaling results in dysregulation of cartilage matrix composition and may transform articular cartilage in a way that it becomes more prone to degenerate.

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Alternative Routes of Administration of the Neuroprotective Pituitary Adenylate Cyclase Activating Polypeptide

Cited by 13 publications

References 0 publications

Stability Test of PACAP in Eye Drops

Stability Test of PACAP in Eye Drops

The Neuroprotective and Biomarker Potential of PACAP in Human Traumatic Brain Injury

Age-related alterations of articular cartilage in pituitary adenylate cyclase–activating polypeptide (PACAP) gene–deficient mice

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