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Collectively, these findings highlight a novel thermoregulatory role for PDE10A in mouse and human adipocytes and promote PDE10A inhibitors as promising candidates for the treatment of obesity and diabetes.
The method proposed for quantification of [(11)C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [(11)C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra.
Studied what regions of the PDE10A gene are transcribed in human putamen and caudate nucleus brain tissue, two sub-regions of the striatum. Surprisingly, twelve novel transcripts were detected, of which three were predicted to be translated into PDE10A proteins with unique N-termini.studies show that there is much more transcript diversity within the PDE10A gene region than initially believed.
The PDE10A gene is currently known to be comprised of 23 exons26 and maps to chromosome 6q26,17, 18 a region previously associated with bipolar disorder.
germline PDE10A mutations associated with hyperkinetic movement disorder
We have demonstrated that de novo dominant mutations in PDE10A are the cause of a unique movement disorder characterized by benign childhood-onset chorea and typical MRI (show C7ORF49 ELISA Kits) abnormalities of the striatum.
cGMP PDE (show ALDH7A1 ELISA Kits) isozymes, PDE5 (show PDE5A ELISA Kits) and 10, are elevated in colon tumor cells compared with normal colonocytes, and inhibitors and siRNAs can selectively suppress colon tumor cell growth
Longitudinal data in a cohort of patients with early Huntington disease (show HTT ELISA Kits) found PDE10 to be a useful biomarker of disease progression.
Lu AF33241 represents a novel PDE2A (show PDE2A ELISA Kits)/PDE10A inhibitor tool which can penetrate the blood brain barrier.
PDE10A activity in medium spiny neurons in Huntington's disease might still be high in critical subcellular compartments, despite the overall striatal PDE10A decrease measured using positron-emission tomography.
Through a combination of pharmacological and genetic tools, study provides convergent evidence of D2 (rather than D1) pathway dominant effects of PDE10A inhibition in rodents
A knock-in mouse model carrying the homologous p.Tyr97Cys variant had decreased striatal PDE10A and also displayed motor abnormalities
Its alteration leads to a cause of Huntington disease (show HTT ELISA Kits).
data show that PDE10A plays a pivotal role in striatal signaling and striatum-mediated salience attribution
findings reveal a dynamic interplay between PDE10A activity, level of neuronal network depolarization and degree of dopaminergic tone in the ability of D1 receptors to facilitate the GABAergic transmission to SNpr neurons.
PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity.
PDE10A-deficient mice showed changes in appetitively as well as aversively motivated responding, and in visuospatial learning and memory, which could not be reduced to neuromotor impairments.
Observed suppression of PDE10A activity significantly inhibits gene expression in the striatum and predicts neuroprotective effects in models of Huntington's disease.
findings suggest that PDE10A is involved in regulating striatal output, possibly by reducing the sensitivity of medium spiny neurons to glutamatergic excitation
PDE10A knockout mice showed a significant change in striatal dopamine turnover, which was accompanied by an enhanced locomotor response to amphetamine
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene.
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
, dJ416F21.1 (phosphodiesterase 10A)
, phosphodiesterase 10A1 (PDE10A1)
, PDE10A2 brain-specific isoform
, dual-substrate cAMP and cGMP, cyclic nucleotide phosphodiesterase
, testis-specific phosphodiesterase PDE10A2