RETRACTED: Pro-inflammatory Effect of Downregulated CD73 Expression in EAE Astrocytes

Zhou, Shumin; Liu, Shuai; Guo, Jie; Kong, Fanting; Chen, Song; Wang, Zhiyun

doi:10.3389/fncel.2019.00233

Cited by 12 publications

(9 citation statements)

References 57 publications

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“…Interestingly, a pro-inflammatory effect of CD73 downregulation in EAE astrocytes was recently demonstrated. In this study, CCPA showed the same effect as Ado on CD73 −/− astrocytes, while other selective AR agonists did not [64].…”

Section: The Beneficial Role Of a 1 Ars In Autoimmunitysupporting

confidence: 44%

Adenosine Signaling in Autoimmune Disorders

Magni

Ceruti

2020

Pharmaceuticals

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The molecular components of the purinergic system (i.e., receptors, metabolizing enzymes and membrane transporters) are widely expressed in the cells of the immune system. Additionally, high concentrations of adenosine are generated from the hydrolysis of ATP in any “danger” condition, when oxygen and energy availability dramatically drops. Therefore, adenosine acts as a retaliatory metabolite to counteract the nucleotide-mediated boost of the immune reaction. Based on this observation, it can be foreseen that the recruitment with selective agonists of the receptors involved in the immunomodulatory effect of adenosine might represent an innovative anti-inflammatory approach with potential exploitation in autoimmune disorders. Quite surprisingly, pro-inflammatory activity exerted by some adenosine receptors has been also identified, thus paving the way for the hypothesis that at least some autoimmune disorders may be caused by a derailment of adenosine signaling. In this review article, we provide a general overview of the roles played by adenosine on immune cells with a specific focus on the development of adenosine-based therapies for autoimmune disorders, as demonstrated by the exciting data from concluded and ongoing clinical trials.

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Section: The Beneficial Role Of a 1 Ars In Autoimmunitysupporting

confidence: 44%

Adenosine Signaling in Autoimmune Disorders

Magni

Ceruti

2020

Pharmaceuticals

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“…This phenomenon was observed not only in peripheral immune cells but also in glial cells in the CNS. Recent studies have demonstrated that genetic removal of astrocytic CD73 blocks AMP-mediated cytokine release from astrocytes [ 258 ]. Badimon et al [ 16 ] recently showed that microglial CD39/CD73-mediated ATP hydrolysis suppresses neuronal activity by activating A 1 adenosine receptor (A 1 R) in a feedback regulatory manner.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of dysregulated adenosine homeostasis in brain disorders with a specific focus on neurodegenerative diseases

Chang

Lin

et al. 2021

J Biomed Sci

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In modern societies, with an increase in the older population, age-related neurodegenerative diseases have progressively become greater socioeconomic burdens. To date, despite the tremendous effort devoted to understanding neurodegenerative diseases in recent decades, treatment to delay disease progression is largely ineffective and is in urgent demand. The development of new strategies targeting these pathological features is a timely topic. It is important to note that most degenerative diseases are associated with the accumulation of specific misfolded proteins, which is facilitated by several common features of neurodegenerative diseases (including poor energy homeostasis and mitochondrial dysfunction). Adenosine is a purine nucleoside and neuromodulator in the brain. It is also an essential component of energy production pathways, cellular metabolism, and gene regulation in brain cells. The levels of intracellular and extracellular adenosine are thus tightly controlled by a handful of proteins (including adenosine metabolic enzymes and transporters) to maintain proper adenosine homeostasis. Notably, disruption of adenosine homeostasis in the brain under various pathophysiological conditions has been documented. In the past two decades, adenosine receptors (particularly A1 and A2A adenosine receptors) have been actively investigated as important drug targets in major degenerative diseases. Unfortunately, except for an A2A antagonist (istradefylline) administered as an adjuvant treatment with levodopa for Parkinson’s disease, no effective drug based on adenosine receptors has been developed for neurodegenerative diseases. In this review, we summarize the emerging findings on proteins involved in the control of adenosine homeostasis in the brain and discuss the challenges and future prospects for the development of new therapeutic treatments for neurodegenerative diseases and their associated disorders based on the understanding of adenosine homeostasis.

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“…7a – e ), or CD73 ( Fig. 4a ), which is expressed by striatal microglia, albeit at levels lower than in striatal neurons, as judged by CD73 mRNA and protein expression 18 , 25 , 35 ( Fig. 4b , Extended Data Fig.…”

mentioning

confidence: 99%

Negative feedback control of neuronal activity by microglia

Badimon

Strasburger

Ayata

et al. 2020

Nature

678

555

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Microglia, the brain’s resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival 1 . Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures. Suppression of neuronal activation by microglia occurs in a highly region-specific fashion and depends on the ability of microglia to sense and catabolize extracellular ATP, which is released upon neuronal activation by neurons and astrocytes. ATP triggers the recruitment of microglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then converted into adenosine by CD73, which is expressed on microglia as well as other brain cells. Microglial sensing of ATP, the ensuing microglia-dependent production of adenosine, and the adenosine-mediated suppression of neuronal responses via the adenosine receptor A 1 R are essential for the regulation of neuronal activity and animal behaviour. Our findings suggest that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease.

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RETRACTED: Pro-inflammatory Effect of Downregulated CD73 Expression in EAE Astrocytes

Cited by 12 publications

References 57 publications

Adenosine Signaling in Autoimmune Disorders

Adenosine Signaling in Autoimmune Disorders

Emerging roles of dysregulated adenosine homeostasis in brain disorders with a specific focus on neurodegenerative diseases

Negative feedback control of neuronal activity by microglia

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