PACAP Signaling in Neuroprotection

Manecka, Destiny-Love; Boukhzar, Loubna; Falluel‐Morel, Anthony; Lihrmann, Isabelle; Anouar, Youssef

doi:10.1007/978-3-319-35135-3_32

Cited by 9 publications

(12 citation statements)

References 91 publications

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“…The neuroprotective mechanism of PACAP is both direct and indirect, via neuronal and non-neuronal cells [ 14 , 18 ]. PACAP acts through its specific G protein-coupled PAC1 receptor, which only binds PACAP, and through the VPAC1 and VPAC2 receptors, which also bind the structurally related vasoactive intestinal peptide (VIP) with similar affinity [ 26 , 27 ]. The neuroprotective signaling is mediated mainly via the PACAP-specific PAC1 receptor [ 24 , 28 ], through which anti-apoptotic and regeneration-promoting effects are mediated.…”

Section: General Overviewmentioning

confidence: 99%

“…However, the involvement of VPAC receptors also seems to be important, mainly conveying anti-inflammatory actions of the peptide. Via receptorial mechanisms, PACAP stimulates cAMP/PKA- (cyclic adenosine monophosphate/protein kinase A) mediated signaling, and also PI3K-pathways (phosphoinositol 3 kinase) and calcium-regulated mechanisms [ 27 , 29 ]. In addition, PACAP transactivates growth factor-related pathways [ 30 ] and penetrates the cell membrane directly, through receptor-independent uptake [ 31 ].…”

Section: General Overviewmentioning

confidence: 99%

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Review on PACAP-Induced Transcriptomic and Proteomic Changes in Neuronal Development and Repair

Rivnyak

Kiss

Tamás

et al. 2018

IJMS

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with widespread occurrence and diverse biological effects. Among its several different effects, of special importance is the action of PACAP on neuronal proliferation, differentiation and migration, and neuroprotection. The neuroprotective mechanism of PACAP is both direct and indirect, via neuronal and non-neuronal cells. Several research groups have performed transcriptomic and proteomic analysis on PACAP-mediated genes and proteins. Hundreds of proteins have been described as being involved in the PACAP-mediated neuroprotection. In the present review we summarize the few currently available transcriptomic data potentially leading to the proteomic changes in neuronal development and protection. Proteomic studies focusing on the neuroprotective role of PACAP are also reviewed and discussed in light of the most intriguing and promising effect of this neuropeptide, which may possibly have future therapeutic potential.

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Section: General Overviewmentioning

confidence: 99%

Section: General Overviewmentioning

confidence: 99%

Review on PACAP-Induced Transcriptomic and Proteomic Changes in Neuronal Development and Repair

Rivnyak

Kiss

Tamás

et al. 2018

IJMS

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“…Although PACAP38-induced PC12 neurite outgrowth was thought to be mediated by the GSK-3 β pathway, previous studies have shown that the signaling cascade from the PACAP receptor PAC1 moves mainly via the AKT pathway, the cAMP/PKA pathway, the cAMP/ERK pathway, and also the PLC/PKC pathway [ 39 ]. CRMP2 is known to be regulated by the PI3 kinase/Akt/GSK-3 β signaling pathway [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanism for PACAP 38-Induced Neurite Outgrowth in PC12 Cells

et al. 2021

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The present research investigates the molecular mechanism of neurite outgrowth (protrusion elongation) under pituitary adenylate cyclase-activating polypeptide (PACAP) 38 treatments using a rat adrenal-derived pheochromocytoma cell line—PC12. This study specifically looks into the regulation of PACAP38-induced collapsing response mediator protein 2 (CRMP2) previously identified in a mouse brain ischemia model and which could be recovered by PACAP38 treatment. Previously, DNA microarray analysis revealed that PACAP 38-mediated neuroprotection involved not only CRMP2 but also pathways related to glycogen synthase kinase-3β (GSK-3β) and other signaling components. Thus, to clarify whether CRMP2 acts directly on PACAP38 or through GSK-3β as part of the mechanism of PACAP38-induced neurite outgrowth, we observed neurite outgrowth in the presence of GSK-3β inhibitors and activators. PC12 cells were treated with PACAP38 being added to the cell culture medium at concentrations of 10−7 M, 10−8 M, and 10−9 M. Post PACAP38 treatment, immunostaining was used to confirm protrusion elongation of the PC12 cells, while RT-PCR, two-dimensional gel electrophoresis in conjunction with Western blotting, and inhibition experiments were performed to confirm the expression of the PACAP gene, its receptors, and downstream signaling components. Our data show that neurite protrusion elongation by PACAP38 (10−7 M) in PC12 cells is mediated through the PAC1-R receptor as demonstrated by its suppression by a specific inhibitor PA-8. Inhibitor experiments suggested that PACAP38-triggered neurite protrusion follows a GSK-3β-regulated pathway, where the AKT and cAMP/ERK pathways are involved and where the inhibition of Rho/Roc could enhance neurite protrusion under PACAP38 stimulation. Although we could not yet confirm the exact role and position of CRMP2 in PACAP38-mediated PC12 cell elongation, it appears that its phosphorylation and dephosphorylation have a correlation with the neurite protrusion elongation through the interplay of CDK5, which needs to be investigated further.

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“…PACAP is also capable of suppressing the production of microglia-derived reactive oxygen species [ 61 ]. Additionally, it activates anti-inflammatory pathways and antioxidant molecules, which strengthen its potency to counteract neuronal damage [ 62 ]. Furthermore, the neuropeptide is shown to play a role in cellular and tissue aging [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations of Nigral Dopamine Levels in Parkinson’s Disease after Environmental Enrichment and PACAP Treatment in Aging Rats

Jungling

Reglődi

Maász

et al. 2021

Life

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The neuroprotective effects of environmental enrichment and PACAP (pituitary adenylate cyclase-activating polypeptide) are well-described in Parkinson’s disease. The aim of our study is to investigate the beneficial effects of these factors in aging parkinsonian rats. Newborn Wistar rats were divided into standard and enriched groups according to their environmental conditions. Standard animals were raised under regular conditions. During the first five postnatal weeks, enriched pups were placed in larger cages with different objects. Aging animals received (1) saline, (2) 6-hydroxidopamine (6-OHDA), or (3) 6-OHDA + PACAP injections into the left substantia nigra (s.n.). On the seventh postoperative day, the left and right s.n. were collected. The s.n. of young and aging unoperated animals were also examined in our experiment. We determined the dopamine (DA) levels by the HPLC-MS technique, while the sandwich ELISA method was used to measure the Parkinson disease protein 7 (PARK7) protein levels. In healthy animals, we found an age-related decrease of DA levels. In aging parkinsonian-enriched rats, the operation did not result in a significant DA loss. PACAP treatment could prevent the DA loss in both the standard and enriched groups. All injured PACAP-treated rats showed remarkably higher protective PARK7 levels. The protective effect of PACAP correlated with the increase of the DA and PARK7 levels.

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PACAP Signaling in Neuroprotection

Cited by 9 publications

References 91 publications

Review on PACAP-Induced Transcriptomic and Proteomic Changes in Neuronal Development and Repair

Review on PACAP-Induced Transcriptomic and Proteomic Changes in Neuronal Development and Repair

Molecular Mechanism for PACAP 38-Induced Neurite Outgrowth in PC12 Cells

Alterations of Nigral Dopamine Levels in Parkinson’s Disease after Environmental Enrichment and PACAP Treatment in Aging Rats

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