Protective effects of PACAP in ischemia

Reglődi, Dóra; Vaczy, Alexandra; Rubio‐Beltrán, Eloísa; MaassenVanDenBrink, Antoinette

doi:10.1186/s10194-018-0845-3

Cited by 46 publications

(39 citation statements)

References 111 publications

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“…It decreases the activity of matrix degrading enzymes in chondrogenic cell cultures during mechanical overload (Szentleleky et al 2019). It also has a protective function in retinopathy of prematurity (Kvarik et al 2016) and ischemic conditions (Reglodi et al 2018b). All of these facts indicate that PACAP can have important functions in fractured bone remodeling and healing.…”

Section: Discussionmentioning

confidence: 99%

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

et al. 2019

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling. Fracturing was 5 mm distal from the proximal articular surface of the tibia and the depth was 0.5 mm. Reproducibility of callus formation was investigated with CT 3, 7, and 21 days after the operation. Absence of PACAP did not alter the alkaline phosphatase (ALP) activation in PACAP KO healing process. In developing callus, the expression of collagen type I increased in wild-type (WT) and PACAP KO mice decreased to the end of healing process. Expression of the elements of BMP signaling was disturbed in the callus formation of PACAP KO mice, as bone morphogenic protein 4 (BMP4) and 6 showed an early reduction in bone regeneration. However, elevated Smad1 expression was demonstrated in PACAP KO mice. Our results indicate that PACAP KO mice show various signs of disturbed bone healing and suggest PACAP compensatory and fine tuning effects in proper bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

et al. 2019

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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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“…Although the focus here is on CGRP, similar considerations may emerge as blockade of PACAP is developed as a therapeutic strategy in migraine . Like CGRP, PACAP is a vasodilator and contributes to peripheral and central pain sensitization.…”

Section: Pituitary Adenylate Cyclase‐activating Polypeptide (Pacap)mentioning

confidence: 99%

“…Like CGRP, PACAP activates adenylyl cyclase and cAMP‐dependent downstream pathways . Not surprisingly, then, in vitro and animal models suggest that PACAP elicits similar neuroprotective processes . These include antiapoptotic signaling, production of BDNF and nitric oxide, adult neurogenesis, and antioxidant defenses .…”

Section: Pituitary Adenylate Cyclase‐activating Polypeptide (Pacap)mentioning

confidence: 99%

CGRP and Brain Functioning: Cautions for Migraine Treatment

Borkum

2019

Headache

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Background Calcitonin gene‐related peptide has emerged as a therapeutic target in migraine. Monoclonal antibodies and small molecule receptor antagonists (gepants) directed against CGRP have been approved or are in Phase II or III clinical trials. For monitoring the long‐term safety of these drugs, it is helpful to consider the role of CGRP in brain functioning. Methods Qualitative review of the preclinical literature on CGRP in brain physiology and pathophysiology. Results Within the brain, CGRP is upregulated by stresses such as ischemia, injury, hyperthermia, and seizure, and activates neuroprotective processes. Thus, CGRP buffers intracellular calcium, triggers antiapoptotic signaling, upregulates a number of neurotrophins (including insulin‐like growth factor‐1/IGF‐1, basic fibroblast growth factor/bFGF, and nerve growth factor/NGF), reduces brain edema, and likely increases antioxidant defenses. When released outside the blood‐brain barrier, CGRP likely protects the endothelium, upregulates growth factor signaling from the endothelium to the brain parenchyma, strengthens the blood‐brain barrier, protects the immune privilege of the brain by inhibiting the movement of neutrophils and monocytes, and facilitates neurogenesis and angiogenesis at stem cell niches. Conclusions CGRP participates in a wide range of neuroprotective processes. In theory, migraineurs with comorbid brain pathology might be at increased risk from CGRP inhibition. However, the extent of compensating processes is unknown and will determine whether these risks materialize in practice.

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Protective effects of PACAP in ischemia

Cited by 46 publications

References 111 publications

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

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

CGRP and Brain Functioning: Cautions for Migraine Treatment

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