Phosphodiesterase 10A (PDE10A) localization in the R6/2 mouse model of Huntington's disease

Leuti, Alessandro; Laurenti, Daunia; Giampà, Carmela; Montagna, Elena; Dato, Clemente; Anzilotti, Serenella; Melone, Mariarosa Anna Beatrice; Bernardi, Giorgio; Fusco, Francesca R.

doi:10.1016/j.nbd.2012.11.016

Cited by 43 publications

(33 citation statements)

References 65 publications

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“…Given this, the above changes are likely to lead to reduced cGMP tone and PKG hypoactivity in sGC-containing MSNs. Further recent studies have reported that PDE10A and PDE1B mRNA and protein are reduced in the striatum in mouse models of HD [73, 74], but see also [75]. Complementary outcomes have been reported in postmortem studies comparing time-matched brain samples from controls and HD patients [76].…”

Section: Introductionmentioning

confidence: 87%

Modulation of striatal neuron activity by cyclic nucleotide signalling and phosphodiesterase inhibition

Threlfell

West

2013

Basal Ganglia

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The cyclic nucleotides cAMP and cGMP are common signaling molecules synthesized in neurons following the activation of adenylyl or guanylyl cyclase. In the striatum, the synthesis and degradation of cAMP and cGMP is highly regulated as these second messengers have potent effects on the activity of striatonigral and striatopallidal neurons. This review will summarize the literature on cyclic nucleotide signaling in the striatum with a particular focus on the impact of cAMP and cGMP on the membrane excitability of striatal medium-sized spiny output neurons (MSNs). The effects of non-selective and selective phosphodiesterase (PDE) inhibitors on membrane activity and synaptic plasticity of MSNs will also be reviewed. Lastly, this review will discuss the implications of the effects PDE modulation on electrophysiological activity of striatal MSNs as it relates to the treatment of neurological disorders such as Huntington’s and Parkinson’s disease.

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Section: Introductionmentioning

confidence: 87%

Modulation of striatal neuron activity by cyclic nucleotide signalling and phosphodiesterase inhibition

Threlfell

West

2013

Basal Ganglia

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“…We chose to study the expression of PDE1B and PDE10A, because both are highly and specifically located in the basal ganglia (Fujishige et al, 1999;Polli and Kincaid, 1994;Soderling et al, 1999), and are affected in extrapyramidal disorders (Giorgi et al, 2011;Leuti et al, 2013;Sancesario et al, 2004). In 6-OHDA lesioned animals, PDE1B is increased and PDE10A is decreased in the striatum of the lesioned side compared with the unlesioned side (Fig.…”

Section: Pde1b and Pde10a In The Striatummentioning

confidence: 99%

Levodopa-induced dyskinesias are associated with transient down-regulation of cAMP and cGMP in the caudate-putamen of hemiparkinsonian rats: Reduced synthesis or increased catabolism?

Sancesario

Morrone

D′Angelo

et al. 2014

Neurochemistry International

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“…Depletion of PDE10A in HD striatum would at first sight seem hard to reconcile with a beneficial effect of PDE10A inhibitors in HD. However, a recent study reported a dramatic increase in PDE10A levels in the perikarya of striatal medium spiny neurons [123] and moreover, we did not observe changes in the expression of this protein in the hippocampus of R6/1 mice compared to controls [101]. Taking together all these results, it is important to determine whether PDE10A levels are affected in HD patients and in in vivo models of HD in the different brain areas and if these alterations are functionally significant in order to choose PDE10A inhibitors for use in clinical trials in HD.…”

Section: Role Of Phosphodiesterasesmentioning

confidence: 94%

Pathogenesis of Huntington’s Disease: How to Fight Excitotoxicity and Transcriptional Dysregulation

Anglada-Huguet¹,

Vidal-Sancho²,

Cabezas-Llobet³

et al. 2017

Huntington's Disease - Molecular Pathogenesis and Current Models

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Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in the exon-1 of the huntingtin (htt) gene. The presence of mutant htt (mhtt) results in multiple physiopathological changes, including protein aggregation, transcriptional deregulation, decreased trophic support, alteration in signaling pathways and excitotoxicity. Indeed, the presence of mhtt induces changes in the activities/levels of different kinases, phosphatases and transcription factors that can impact on cell survival. Many studies have provided evidence that transcription may be a major target of mhtt, as gene dysregulation occurs before the onset of symptoms. The greatest number of downregulated genes in HD has led to test the ability of a large number of compounds to restore gene transcription in mouse models of HD. On the other hand, mhtt engenders multiple cellular dysfunctions including an increase of pathological glutamate-mediated excitotoxicity. For that reason, targeting the excess of glutamate has been the goal for many promising drugs leading to clinical trials. Although advances in developing effective therapies are evident, currently, there is no known cure for HD and existing symptomatic treatments are limited.

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Phosphodiesterase 10A (PDE10A) localization in the R6/2 mouse model of Huntington's disease

Cited by 43 publications

References 65 publications

Modulation of striatal neuron activity by cyclic nucleotide signalling and phosphodiesterase inhibition

Modulation of striatal neuron activity by cyclic nucleotide signalling and phosphodiesterase inhibition

Levodopa-induced dyskinesias are associated with transient down-regulation of cAMP and cGMP in the caudate-putamen of hemiparkinsonian rats: Reduced synthesis or increased catabolism?

Pathogenesis of Huntington’s Disease: How to Fight Excitotoxicity and Transcriptional Dysregulation

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