How do adenosine A2A receptors regulate motor function?

Mori, Akihisa

doi:10.1016/j.parkreldis.2020.09.025

Cited by 34 publications

(32 citation statements)

References 98 publications

(131 reference statements)

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“…Adenosine regulates multiple physiological and pathophysiological processes, by acting both through G-protein coupled adenosine receptors and intracellularly. It modulates neuronal plasticity (Sebastiao and Ribeiro, 2015), astrocytic activity (Agostinho et al, 2020), learning and memory (Chen, 2014;Simoes et al, 2016;Bannon et al, 2017;Perrier et al, 2019;Temido-Ferreira et al, 2019;Zhang et al, 2020), food intake (Kola, 2008), motor function (Mori, 2020), sleep/wake cycle (Donlea et al, 2017;Lazarus et al, 2019), pain (Vincenzi et al, 2020), immunosupression (Vijayan et al, 2017), proliferation (Jacobson et al, 2019), and aging (Costenla et al, 2011). Adenosine is involved in ischemia and stroke (Williams-Karnesky and Stenzel-Poore, 2009;Melani et al, 2014;Pereira-Figueiredo et al, 2021), epilepsy (Boison and Jarvis, 2020;Tescarollo et al, 2020), and neurodegenerative pathologies such as Parkinson's disease (PD) (Fredholm and Svenningsson, 2020;Glaser et al, 2020), Alzheimer's disease (AD) (Rahman, 2009;Cunha and Agostinho, 2010;Cellai et al, 2018), amyotrophic lateral sclerosis (ALS) (Ng et al, 2015;Sebastiao et al, 2018), and Huntington's disease (HD) (Lee and Chern, 2014).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5′-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington’s disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits.

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Section: Introductionmentioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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“…Additionally expressed in the globus pallidus (external), nucleus accumbens, olfactory tubercle [17,18,41]. Expressed in lower levels in the hippocampus, thalamus, cerebellum, cerebral cortex [38,[42][43][44] and spinal cord motor neurons [36,41,45].…”

Section: Adenosine Receptorsmentioning

confidence: 99%

“…Discovery of physiological significance of A 2A Rs in the MSN and establishing the mechanism of action for A 2A R antagonism in PD therapy [43]. v.…”

Section: Adenosine Receptorsmentioning

confidence: 99%

How Are Adenosine and Adenosine A2A Receptors Involved in the Pathophysiology of Amyotrophic Lateral Sclerosis?

et al. 2021

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Adenosine is extensively distributed in the central and peripheral nervous systems, where it plays a key role as a neuromodulator. It has long been implicated in the pathogenesis of progressive neurogenerative disorders such as Parkinson’s disease, and there is now growing interest in its role in amyotrophic lateral sclerosis (ALS). The motor neurons affected in ALS are responsive to adenosine receptor function, and there is accumulating evidence for beneficial effects of adenosine A2A receptor antagonism. In this article, we focus on recent evidence from ALS clinical pathology and animal models that support dynamism of the adenosinergic system (including changes in adenosine levels and receptor changes) in ALS. We review the possible mechanisms of chronic neurodegeneration via the adenosinergic system, potential biomarkers and the acute symptomatic pharmacology, including respiratory motor neuron control, of A2A receptor antagonism to explore the potential of the A2A receptor as target for ALS therapy.

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“…Modifying the activity of the indirect pathway SPNs by blocking A 2A receptors reduces the release of gamma-aminobutyric acid from the SPNs to the external globus pallidus (GPe), which leads to normalization of GPe activity. This in turn normalizes the activity of the subthalamic nucleus, the internal globus pallidus and the motor thalamus, which improves parkinsonian motor symptoms [8].…”

Section: Introductionmentioning

confidence: 98%

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

Shimo

Maeda

Chiu

et al. 2021

Parkinsonism & Related Disorders

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The non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A 2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD. Methods: Patients with PD and ≥1 NMS and 'wearing-off' with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual subitems scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model. Results: Overall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score. Conclusion: NMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.

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How do adenosine A2A receptors regulate motor function?

Cited by 34 publications

References 98 publications

Metabolic Aspects of Adenosine Functions in the Brain

Metabolic Aspects of Adenosine Functions in the Brain

How Are Adenosine and Adenosine A2A Receptors Involved in the Pathophysiology of Amyotrophic Lateral Sclerosis?

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

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