Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice

Puzzo, Daniela; Loreto, Carla; Giunta, Salvatore; Musumeci, Giuseppe; Frasca, Giampiero; Podda, Maria Vittoria; Arancio, Ottavio; Palmeri, Agostino

doi:10.1016/j.neurobiolaging.2013.09.002

Cited by 78 publications

(56 citation statements)

References 110 publications

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“…It has been shown that Sildenafil reduces apoptosis in the brain and weakens the effect of learning and memory i Q2 mpairments in different mouse aging models (Puzzo et al, 2014;Orejana et al, 2015), elevates the pain threshold level of diabetic neuropathic mice , improves neurogenesis (Zhang et al, 2002) and recovers the brain plasticity of rats after a stroke (Zhang et al, 2005). The protective effects of sildenafil have also been demonstrated in MS animal models.…”

Section: Introductionmentioning

confidence: 99%

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

et al. 2015

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Section: Introductionmentioning

confidence: 99%

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

et al. 2015

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“…This study also showed that sildenafil increased the expression of the antiapoptotic proteins Bcl-2 and Bcl-xL and reduced cell death. The effect of sildenafil on the decrease of apoptosis (through reduction of proapoptotic proteins Bax and caspase-3 expression and increasing the antiapoptotic protein Bcl-2) has also been demonstrated in physiological aging mouse model [149] (Figure 4B).…”

Section: Strokementioning

confidence: 71%

“…However, it is not clear if sildenafil induces oligodendrogenesis or if it inhibits cell death/apoptosis or both. Myelin protection and oligodendrocyte proliferation have also been demonstrated in ischemic models [147,148], and several studies showed that PDE5-Is inhibit apoptosis in central neurological disease models [122,148,149].…”

Section: Multiple Sclerosismentioning

confidence: 99%

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

Peixoto¹,

Nunes²,

Rapôso³

2017

Mechanisms of Neuroinflammation

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The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling appears to play a key role in inhibiting neuroinflammation and preventing the activation of a proapoptotic pathway, thereby promoting neural cell survival. In addition, evidence indicates that cGMP/protein kinase G (PKG) pathway is involved in the modulation of glial cell activity. Phosphodiesterase 5 (PDE5), which hydrolyzes cGMP in the inactive form, 5ʹGMP, is present throughout the body and brain and has emerged as a potential therapeutic target for diseases related to neuroinflammatory and neurodegenerative processes, since their inhibition leads to accumulation of cGMP. The objective of this chapter is to review current knowledge of NO/cGMP signaling pathways on neuroinflammation and the potential therapeutic use of PDE5 inhibitors (PDE5-Is) in neurological diseases. The extensive, while recent, literature on the effects of PDE-Is on Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and stroke has been reviewed.

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“…Over the past few years, our group and others have demonstrated that treatment with PDE5-Is rescues synaptic and memory deficits in the APP/ PS1 mouse model of AD, restoring phospho-CREB levels and decreasing Aβ load [112,128]. The PDE5-I sildenafil also exerts the same beneficial effect in a physiological mouse model of aging [113], where it also inhibits apoptosis and increases antiapoptotic molecules Bcl2 and BDNF [129].…”

Section: The Erk1/2 Mitogen-activated Protein Kinase Pathwaymentioning

confidence: 95%

Synaptic Therapy in Alzheimer's Disease: A CREB-centric Approach

et al. 2015

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Therapeutic attempts to cure Alzheimer's disease (AD) have failed, and new strategies are desperately needed. Motivated by this reality, many laboratories (including our own) have focused on synaptic dysfunction in AD because synaptic changes are highly correlated with the severity of clinical dementia. In particular, memory formation is accompanied by altered synaptic strength, and this phenomenon (and its dysfunction in AD) has been a recent focus for many laboratories. The molecule cyclic adenosine monophosphate response element-binding protein (CREB) is at a central converging point of pathways and mechanisms activated during the processes of synaptic strengthening and memory formation, as CREB phosphorylation leads to transcription of memory-associated genes. Disruption of these mechanisms in AD results in a reduction of CREB activation with accompanying memory impairment. Thus, it is likely that strategies aimed at these mechanisms will lead to future therapies for AD. In this review, we will summarize literature that investigates 5 possible therapeutic pathways for rescuing synaptic dysfunction in AD: 4 enzymatic pathways that lead to CREB phosphorylation (the cyclic adenosine monophosphate cascade, the serine/threonine kinases extracellular regulated kinases 1 and 2, the nitric oxide cascade, and the calpains), as well as histone acetyltransferases and histone deacetylases (2 enzymes that regulate the histone acetylation necessary for gene transcription).

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Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice

Cited by 78 publications

References 110 publications

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

Synaptic Therapy in Alzheimer's Disease: A CREB-centric Approach

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