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Hyperkinetic Movement Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Morales-Briceno Hugo, Victor S.C. Fung, Annu Aggarwal, Philip Thompson
Striatal lesion syndromes associated with chorea: PDE10A mutations.PDE2A mutations.VPS13D mutations.32
Interactions between genetic variants and near-work activities in incident myopia in schoolchildren: a 4-year prospective longitudinal study
Published in Clinical and Experimental Optometry, 2023
Yaoyao Lin, Dandan Jiang, Chunchun Li, Xiaoqiong Huang, Haishao Xiao, Linjie Liu, Yanyan Chen
Myopia is the result of a combination of genetic and environmental factors; thus, interactions between genes and the environment (G × E) may account for more of the refractive errors.10 Several studies in adults have demonstrated G × E interactions, particularly with education, for refractive errors.11–13 Recently, another larger GWAS study showed that PDE10A rs12206610, AREG rs12511037 and GABRR1 rs13215566 exhibited strong interactions with education in Asian adults.10PDE10A is mostly expressed in the retina.14 The gene encodes phosphodiesterase, hydrolysing both cAMP and cGMP to monophosphate.15PDE10A protein levels display circadian patterns in retinal photoreceptors, suggesting that it has a potential role in the visual process.16AREG is mostly expressed in the choroid/retinal pigment epithelium (RPE) and is involved in extracellular matrix remodelling.17
Challenges in the clinical development of non-D2 compounds for schizophrenia
Published in Current Medical Research and Opinion, 2023
Seth C. Hopkins, Robert Lew, Courtney Zeni, Kenneth S. Koblan
The “non-D2” category included non-D2 compounds which do not occupy, directly interact with, or block the dopamine D2 receptor; however, many of them may still indirectly affect dopamine neurotransmission. For example, serotonergic compounds (5-HT2A antagonists, 5-HT1A partial agonists) increase prefrontal dopamine levels via mesocortical neurons20,21. Conversely, phosphodiesterase (PDE10a) inhibitors alter dopamine receptor signaling leading to inhibition of dopamine neurotransmission, particularly in the basal ganglia where PDE10a is expressed22. Agonists and positive allosteric modulators at mGluR2 and mGluR5 receptors attenuate DA release in the nucleus accumbens23. Lastly, drugs with TAAR1/5-HT1a agonist activity, such as ulotaront, are thought to modulate dopamine, serotonin, and glutamate neurotransmission, as well as affecting dopamine synthesis14,24.
Quetiapine and novel PDE10A inhibitors potentiate the anti-BuChE activity of donepezil
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Joanna Sikora, Maria Podsiedlik, Tadeusz Pietras, Marcin Kosmalski, Mikołaj Matłoka, Rafał Moszczyński-Petkowski, Maciej Wieczorek, Magdalena Markowicz-Piasecka
The study also examines two novel compounds which primarily act by the inhibition of phosphodiesterase PDE10A. PDEs participate in many signalling processes, as they hydrolyse two crucial signalling molecules: cAMP and cGMP43. During the past 30 years, the issue of PDE distribution, substrate specificity, regulatory mechanisms and inhibition has constituted an active field of research. DeNinno43 describes the major advances in the field of PDEs which include identification of subtypes, and isoforms of PDEs, and understanding of their function43. Interest in PDEs has grown since the approval of moderately selective PDE5 inhibitors such as sildenafil, and tadalafil43,44. Numerous studies indicate that PDE inhibitors present a wide range of pharmacological activities, including anti-inflammatory, anti-oxidant, vasodilator, anti-cancer, and neuroprotective properties, suggesting that they can be used as potential drugs for the treatment of respiratory tract diseases, cardiovascular system diseases, depression, dementia, and PD44–47.