Intracellular compartmentation of cAMP promotes neuroprotection and regeneration of CNS neurons

Cameron, Evan G.; Kapiloff, Michael S.

doi:10.4103/1673-5374.200797

Cited by 15 publications

(14 citation statements)

References 10 publications

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“…Post‐translational modification of nNOS on Ser‐1412 by protein kinase A (PKA)‐mediated phosphorylation constitutes a major regulatory mechanism for NO generation in the penis and MPG . Neuronal stimulation, presumably through the increase in intracellular calcium and adenylate cyclase activation, causes an increase in intracellular cAMP that activates PKA , which phosphorylates nNOS at Ser‐1412, stimulating nNOS catalytic activity . This phospho‐modification lasts longer than the neuronal calcium transient, thus contributing to both the initiation and maintenance phases of erection .…”

Section: Introductionmentioning

confidence: 99%

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

et al. 2017

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Objectives To evaluate nNOS phosphorylation, nNOS uncoupling, and oxidative stress in the penis and major pelvic ganglia (MPG), before and after the administration of the cAMP-dependent protein kinase A (PKA) agonist colforsin in a rat model of bilateral cavernous nerve injury (BCNI) which mimics nerve injury following prostatectomy. Materials and Methods Adult male Sprague–Dawley rats were divided into BCNI and sham groups. Each group included 2 subgroups: vehicle and colforsin (0.1 mg/kg/day i.p.). After 3 days, erectile function (intracavernosal pressure) was measured and penes and MPG were collected for molecular analyses of phospho(P)-nNOS (Ser-1412 and Ser-847), total nNOS, nNOS uncoupling, binding of neuronal nitric oxide synthase (PIN) to nNOS, gp91phox subunit of NADPH oxidase, active caspase 3, PKA catalytic subunit alpha (PKA-Cα) (by Western blot) and oxidative stress (hydrogen peroxide [H2O2] and superoxide by Western blot and microdialysis method). Results Erectile function was decreased 3 days after BCNI and normalized by colforsin. nNOS phosphorylation on both positive (Ser-1412) and negative (Ser-847) regulatory sites, and nNOS uncoupling, were increased after BCNI in the penis and MPG and normalized by colforsin. Hydrogen peroxide and total ROS productions were increased in the penis after BCNI and normalized by colforsin. Protein expression of gp91phox was increased in the MPG after BCNI and was normalized by colforsin treatment. Binding of PIN to nNOS was increased in the penis after BCNI and was normalized by colforsin treatment. Protein expression of active Caspase 3 was increased in the MPG after BCNI and was normalized by colforsin treatment. Protein expression of PKA-Cα was decreased in the penis after BCNI and normalized by colforsin. Conclusion Collectively, BCNI impairs nNOS function in the penis and MPG by mechanisms involving its phosphorylation and uncoupling in association with increased oxidative stress, resulting in erectile dysfunction. PKA activation by colforsin reverses these molecular changes and preserves penile erection in the face of BCNI.

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Section: Introductionmentioning

confidence: 99%

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

et al. 2017

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“…After activation of JAK, STAT family members make homodimers or heterodimers which regulate specific genes involved in the survival and regeneration of the optic nerve axons. The cAMP signaling is activated by electrical activity and enhances the regenerative effect of several neurotrophic factors [93]. The downstream of cAMP signaling includes protein kinase A (PKA) and exchange protein activated by cAMP (EPAC).…”

Section: Intrinsic Survival and Regenerative Pathways For Optic Nerve Regenerationmentioning

confidence: 99%

“…Other intrinsic regenerative genes and pathways include Wnt signaling [114], Lin28 [115], Sry-related high-mobility-box 11 [116], Krüppel-like factor 4/9 [117], histone deacetylase [118], c-myc [119], and cAMP [93,120]. However, a single manipulation of these pathways or these genes is not enough for promoting long-lasting optic nerve regeneration in vivo.…”

Section: Intrinsic Survival and Regenerative Pathways For Optic Nerve Regenerationmentioning

confidence: 99%

The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina

Oshitari

2021

IJMS

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Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and vascular cells. An impairment of these neurovascular units causes both neuronal and vascular abnormalities in diabetic retinopathy. More specifically, neuronal abnormalities including neuronal cell death and axon degeneration are irreversible changes that are directly related to the vision reduction in diabetic patients. Thus, establishment of neuroprotective and regenerative therapies for diabetic neuropathy in the retina is an emergent task for preventing the blindness of patients with diabetic retinopathy. This review focuses on the pathogenesis of the neuronal abnormalities in diabetic retina including glial abnormalities, neuronal cell death, and axon degeneration. The possible molecular cell death pathways and intrinsic survival and regenerative pathways are also described. In addition, therapeutic approaches for diabetic neuropathy in the retina both in vitro and in vivo are presented. This review should be helpful for providing clues to overcome the barriers for establishing neuroprotection and regeneration of diabetic neuropathy in the retina.

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“…However, the mechanism by which cAMP controls these signaling pathways is not fully understood. [ 28 ]…”

Section: The Effect Of Electrical Stimulation On Triggering the Signamentioning

confidence: 99%

“…However, the mechanism by which cAMP controls these signaling pathways is not fully understood. [28] with low stretchability to endure the pressure changes in the intracranial area restricts the application of traditional scaffolds. To ideally repair brain injuries, it is necessary to use biomaterials with proper mechanical strength, elasticity, and stretchability to protect brain tissue and to tolerate the pressure changes in crania defects.…”

Section: The Effect Of Electrical Stimulation On Triggering the Signamentioning

confidence: 99%

Conductive Biomaterials as Substrates for Neural Stem Cells Differentiation towards Neuronal Lineage Cells

Farokhi

Mottaghitalab

Saeb

et al. 2020

Macromolecular Bioscience

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The injuries and defects in the central nervous system are the causes of disability and death of an affected person. As of now, there are no clinically available methods to enhance neural structural regeneration and functional recovery of nerve injuries. Recently, some experimental studies claimed that the injuries in brain can be repaired by progenitor or neural stem cells located in the neurogenic sites of adult mammalian brain. Various attempts have been made to construct biomimetic physiological microenvironment for neural stem cells to control their ultimate fate. Conductive materials have been considered as one the best choices for nerve regeneration due to the capacity to mimic the microenvironment of stem cells and regulate the alignment, growth, and differentiation of neural stem cells. The review highlights the use of conductive biomaterials, e.g., polypyrrole, polyaniline, poly(3,4‐ethylenedioxythiophene), multi‐walled carbon nanotubes, single‐wall carbon nanotubes, graphene, and graphite oxide, for controlling the neural stem cells activities in terms of proliferation and neuronal differentiation. The effects of conductive biomaterials in axon elongation and synapse formation for optimal repair of central nervous system injuries are also discussed.

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Intracellular compartmentation of cAMP promotes neuroprotection and regeneration of CNS neurons

Cited by 15 publications

References 10 publications

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina

Conductive Biomaterials as Substrates for Neural Stem Cells Differentiation towards Neuronal Lineage Cells

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