The Adenosinergic Signaling: A Complex but Promising Therapeutic Target for Alzheimer’s Disease

Cellai, Lucrezia; Carvalho, Kevin; Faivre, Émilie; Deleau, Aude; Vieau, Didier; Buée, Luc; Blum, David; Meriaux, Céline; Gómez-Murcia, Victoria

doi:10.3389/fnins.2018.00520

Cited by 40 publications

(23 citation statements)

References 117 publications

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“…Moreover, it has been demonstrated that interaction between cholinergic and glutamatergic transmission is involved in Ca 2+ -dependent neuroprotection [ 56 ]. The glutamatergic system is controlled by various mediators, including adenosine and ACh [ 56 , 57 , 58 ]. In AD, there is a decrease in the number of the N-methyl-D-aspartate (NMDA) receptors resulting in an imbalance between synaptic and extrasynaptic NMDA receptors [ 59 , 60 ].…”

Section: Alzheimer’s Disease (Ad)mentioning

confidence: 99%

Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies

et al. 2021

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Alzheimer’s disease (AD) is the most common type of dementia leading to progressive memory loss and cognitive impairment. Considering that pharmacological treatment options for AD are few and not satisfactory, increasing attention is being paid to dietary components that may affect the development of the disease. Such a dietary component may be caffeine contained in coffee, tea or energy drinks. Although epidemiological data suggest that caffeine intake may counteract the development of cognitive impairment, results of those studies are not conclusive. The aim of the present study is to review the existing experimental studies on the efficacy of caffeine against AD and AD-related cognitive impairment, focusing on the proposed protective mechanisms of action. In conclusion, the reports of studies on experimental AD models generally supported the notion that caffeine may exert some beneficial effects in AD. However, further studies are necessary to elucidate the role of caffeine in the effects of its sources on cognition and possibly AD risk.

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Section: Alzheimer’s Disease (Ad)mentioning

confidence: 99%

Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies

et al. 2021

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“…There is also an epidemiological inverse correlation of caffeine ingestion with Alzheimer's disease (AD) (Cellai et al, 2018;Cunha, 2016).…”

Section: Naturally Occurring Alkylxanthines As the Prototypical Adenosine Receptor Antagonists And Their Therapeutic Usementioning

confidence: 99%

Adenosine A_2A receptor antagonists: from caffeine to selective non‐xanthines

Jacobson

Gao

Matricon

et al. 2020

British J Pharmacology

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Inhibition of A 2A receptors is one of caffeine's principal effects and we now understand this interaction at the atomic level. The A 2A receptor has become a prototypical example of utilizing high-resolution structures of GPCRs for the rational design of chemically diverse drug molecules. The previous focus on discovery of selective A 2A receptor antagonists for neurodegenerative diseases has expanded to include immunotherapy for cancer, and clinical trials have ensued. | INTRODUCTIONCaffeine (1,3,7-trimethylxanthine; Table 1, compound 1), found in coffee, tea, cola, chocolate, and other foods, is the most widely ingested drug substance (Reyes & Cornelis, 2018). The boost in focus, alertness, and enhanced mood from a cup of morning coffee is essential for many in the Western world. Annual consumption of caffeinecontaining beverages average 348 L per capita in North America, 200 L per capita in Europe, although less in other regions (Reyes & Cornelis, 2018). Coffee contains dozens of pharmacologically active substances, among them are the alkylxanthines, principally caffeine, and antioxidant polyphenols such as the catechol derivative caffeic

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“…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). Extracellular adenosine, interacting with P1 receptors (A1R, A2AR, A2BR, and A3R) regulates metabolism through different signaling pathways.…”

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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The Adenosinergic Signaling: A Complex but Promising Therapeutic Target for Alzheimer’s Disease

Cited by 40 publications

References 117 publications

Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies

Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies

Adenosine A_2A receptor antagonists: from caffeine to selective non‐xanthines

Metabolic Aspects of Adenosine Functions in the Brain

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The Adenosinergic Signaling: A Complex but Promising Therapeutic Target for Alzheimer’s Disease

Cited by 40 publications

References 117 publications

Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies

Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies

Adenosine A2A receptor antagonists: from caffeine to selective non‐xanthines

Metabolic Aspects of Adenosine Functions in the Brain

Contact Info

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Adenosine A_2A receptor antagonists: from caffeine to selective non‐xanthines