Characterizations of a synthetic pituitary adenylate cyclase-activating polypeptide analog displaying potent neuroprotective activity and reduced in vivo cardiovascular side effects in a Parkinson's disease model

Lamine, Asma; Létourneau, Myriam; Doan, Ngoc Duc; Maucotel, Julie; Couvineau, Alain; Vaudry, Hubert; Chatenet, David; Vaudry, David; Fournier, Alain

doi:10.1016/j.neuropharm.2015.05.014

Cited by 45 publications

(32 citation statements)

References 54 publications

(83 reference statements)

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“…Recent data indicate that a synthetic PACAP analog, Ac‐[Phe(pI)6, Nle17]PACAP(1‐27), mimics the neuroprotective action of PACAP against 1‐methyl‐4‐phenylpyridinium (MPP+) toxicity on SH‐SY5Y neuroblastoma cells (Lamine et al . ). As intravenous injections of the analog induce potent neuroprotection in a mouse model of Parkinson's disease (Lamine et al .…”

Section: Discussionmentioning

confidence: 97%

“…As intravenous injections of the analog induce potent neuroprotection in a mouse model of Parkinson's disease (Lamine et al . ), the development of specific PACAP analogs, that would selectively promote the glioprotective and anti‐oxidative proprieties of PACAP, might prove useful for the treatment of ischemia and neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

“…The fact that the antiapoptotic action of PACAP is likely mediated through PAC1 receptor is of particular interest. Recent data indicate that a synthetic PACAP analog, Ac-[Phe(pI)6, Nle17]PACAP(1-27), mimics the neuroprotective action of PACAP against 1methyl-4-phenylpyridinium (MPP+) toxicity on SH-SY5Y neuroblastoma cells (Lamine et al 2015). As intravenous injections of the analog induce potent neuroprotection in a mouse model of Parkinson's disease (Lamine et al 2015), the development of specific PACAP analogs, that would selectively promote the glioprotective and anti-oxidative proprieties of PACAP, might prove useful for the treatment of ischemia and neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase‐activating polypeptide against hydrogen peroxide‐induced oxidative damages in cultured rat astrocytes

Douiri

Bahdoudi

Hamdi

et al. 2016

Journal of Neurochemistry

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Astroglial cells possess an array of cellular defense mechanisms, including superoxide dismutase (SOD) and catalase antioxidant enzymes, to prevent damages caused by oxidative stress. Nevertheless, astroglial cell viability and functionality can be affected by significant oxidative stress. We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent glioprotective agent that prevents hydrogen peroxide (H 2 O 2 )-induced apoptosis in cultured astrocytes. The purpose of this study was to investigate the potential protective effect of PACAP against oxidative-generated alteration of astrocytic antioxidant systems.Incubation of cells with subnanomolar concentrations of PACAP inhibited H 2 O 2 -evoked reactive oxygen species accumulation, mitochondrial respiratory burst, and caspase-3 mRNA level increase. PACAP also stimulated SOD and catalase activities in a concentration-dependent manner, and counteracted the inhibitory effect of H 2 O 2 on the activity of these two antioxidant enzymes. The protective action of PACAP against H 2 O 2 -evoked inhibition of antioxidant systems in astrocytes was protein kinase A, PKC, and MAP-kinase dependent. In the presence of H 2 O 2 , the SOD blocker NaCN and the catalase inhibitor 3-aminotriazole, both suppressed the protective effects of PACAP on SOD and catalase

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase‐activating polypeptide against hydrogen peroxide‐induced oxidative damages in cultured rat astrocytes

Douiri

Bahdoudi

Hamdi

et al. 2016

Journal of Neurochemistry

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“…Among the well-established and most intensively studied actions are PACAP’s neurotrophic and neuroprotective effects. PACAP has been shown to protect neurons against various noxious stimuli in vitro and in vivo [6,7,8] For example, PACAP is protective in traumatic brain [9] and spinal cord injury [10], in global and focal cerebral ischemia [6], in models of Huntington’s disease [11], and in Parkinson’s disease [12,13,14]. …”

Section: Introductionmentioning

confidence: 99%

Passage through the Ocular Barriers and Beneficial Effects in Retinal Ischemia of Topical Application of PACAP1-38 in Rodents

Werling

Banks

Salameh

et al. 2017

IJMS

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The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has two active forms, PACAP1-27 and PACAP1-38. Among the well-established actions are PACAP’s neurotrophic and neuroprotective effects, which have also been proven in models of different retinopathies. The route of delivery is usually intravitreal in studies proving PACAP’s retinoprotective effects. Recently, we have shown that PACAP1-27 delivered as eye drops in benzalkonium-chloride was able to cross the ocular barriers and exert retinoprotection in ischemia. Since PACAP1-38 is the dominant form of the naturally occurring PACAP, our aim was to investigate whether the longer form is also able to cross the barriers and exert protective effects in permanent bilateral common carotid artery occlusion (BCCAO), a model of retinal hypoperfusion. Our results show that radioactive PACAP1-38 eye drops could effectively pass through the ocular barriers to reach the retina. Routine histological analysis and immunohistochemical evaluation of the Müller glial cells revealed that PACAP1-38 exerted retinoprotective effects. PACAP1-38 attenuated the damage caused by hypoperfusion, apparent in almost all retinal layers, and it decreased the glial cell overactivation. Overall, our results confirm that PACAP1-38 given in the form of eye drops is a novel protective therapeutic approach to treat retinal diseases.

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“…A synthetic analog of PACAP showed neuroprotection in MPP + -induced SHSY-5Y cells and MPTP-injected mice. It restored the expression of tyrosine hydroxylase in Substantia nigra and modulated the inflammatory response [99]. Another peptide, called vasoactive intestinal peptide (VIP), can also inhibit the expression of pro-inflammatory cytokines from LPS-activated cultured microglia [100].…”

Section: The Role Of Anti-inflammatory Compounds In Neuroinflammationmentioning

confidence: 99%

Inflammation: Role in Parkinson's Disease and Target for Therapy

Flood¹,

Arbabzada²,

Sharma³

2016

Challenges in Parkinson's Disease

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Evidence is now overwhelming that inflammation is a central process in the pathogenesis of progressive Parkinson's disease PD . The hallmark of this neuroinflammation is the activation of microglial cells and the secondary role of adaptive immunity in both the familial and idiopathic forms of PD, leading to the loss of dopamine-producing cells within the Substantia nigra. This activation is characterized by the oxidative stress response, production of inflammatory mediators, recruitment and activation of immune effector cells which create a toxic environment for dopaminergic neurons, and in forming a continuous cycle of inflammatory responses that result in chronic neuroinflammation and progressive neurodegeneration. This chapter focuses on the different components of the inflammatory response that are involved in Dopamine-neurodegeneration, the evidence for inflammation in different forms of PD, and the role of inflammation in the various animal models of PD. Finally, we provide current evidence that targeting this inflammation with a number of anti-inflammatory therapies can be an effective way to halt the progression of chronic neuroinflammation-induced PD.

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Characterizations of a synthetic pituitary adenylate cyclase-activating polypeptide analog displaying potent neuroprotective activity and reduced in vivo cardiovascular side effects in a Parkinson's disease model

Cited by 45 publications

References 54 publications

Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase‐activating polypeptide against hydrogen peroxide‐induced oxidative damages in cultured rat astrocytes

Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase‐activating polypeptide against hydrogen peroxide‐induced oxidative damages in cultured rat astrocytes

Passage through the Ocular Barriers and Beneficial Effects in Retinal Ischemia of Topical Application of PACAP1-38 in Rodents

Inflammation: Role in Parkinson's Disease and Target for Therapy

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