Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves disease phenotypes in a mouse model of amyotrophic lateral sclerosis

Experimental Neurology
Seng Kah NgYongjie Yang

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease in which the majority of upper and lower motor neurons are degenerated. Despite intensive efforts to identify drug targets and develop neuroprotective strategies, effective therapeutics for ALS remains unavailable. The identification and characterization of novel targets and pathways remain crucial in the development of ALS therapeutics. Adenosine is a major neuromodulator that actively regulates synaptic transmission. Interestingly, adenosine levels are significantly elevated in the cerebrospinal fluid (CSF) of progressing human ALS patients. In the current study, we showed that adenosine 2a receptor (A2aR), but not adenosine 1 receptor (A1R), is highly enriched in spinal (motor) neurons. A2aR expression is also selectively increased at the symptomatic onset in the spinal cords of SOD1G93A mice and end-stage human ALS spinal cords. Interestingly, we found that direct adenosine treatment is sufficient to induce embryonic stem cell-derived motor neuron (ESMN) cell death in cultures. Subsequent pharmacological inhibition and partial genetic ablation of A2aR (A2aR(+/-)) significantly protect ESMN from SOD1G93A(+) astrocyte-induced cell death and...Continue Reading

References

Jul 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·L O Trussell, M B Jackson
Jul 3, 1998·European Journal of Pharmacology·J Sawynok
Nov 21, 2001·Nature Reviews. Neuroscience·D W Cleveland, J D Rothstein
Jun 3, 2006·Science·Séverine BoilléeDon W Cleveland
Sep 8, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jelena Mojsilovic-PetrovicRobert G Kalb
Jan 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John D CahoyBen A Barres
Feb 5, 2008·Nature Neuroscience·Koji YamanakaDon W Cleveland
Jun 28, 2008·Pflügers Archiv : European journal of physiology·Nobuyuki MiyazakiMunehito Yoshida
Feb 20, 2009·The Journal of Comparative Neurology·Frederico A C AzevedoSuzana Herculano-Houzel
Sep 19, 2009·Cell Death and Differentiation·D BoisonB B Fredholm
Dec 3, 2009·The Journal of Cell Biology·Hristelina IlievaDon W Cleveland
Aug 6, 2011·Human Molecular Genetics·Jinbin ZhaiRobert Gordon Kalb
Oct 3, 2012·Glia·Tamara Blutstein, Philip G Haydon
Jan 31, 2013·Journal of Neuroscience Research·Rosa Luisa PotenzaPatrizia Popoli
May 18, 2013·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Fabrizio VincenziKatia Varani
Aug 6, 2013·Molecules and Cells·Hyung Wook NamDoo-Sup Choi
Feb 7, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hibiki KawamataYongjie Yang

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Citations

May 20, 2016·The Journal of Pharmacology and Experimental Therapeutics·Guilherme Carneiro MontesGisele Zapata-Sudo
Jul 2, 2016·Journal of Neurochemistry·Rodrigo A Cunha
Nov 29, 2016·PloS One·Gabriela Hurtado-AlvaradoBeatriz Gómez-González
Mar 21, 2017·CNS Neuroscience & Therapeutics·Mahshad Kolahdouzan, Mazen J Hamadeh
Oct 11, 2017·Frontiers in Pharmacology·Geoffrey Burnstock
May 2, 2018·Frontiers in Pharmacology·Ana M SebastiãoJoaquim A Ribeiro
Jan 31, 2019·Brain : a Journal of Neurology·Scott P AllenPamela J Shaw
Oct 30, 2019·Life Science Alliance·Veronica GranatieroHibiki Kawamata
Nov 18, 2018·International Journal of Molecular Sciences·Mercedes Garcia-GilMaria Grazia Tozzi
Feb 14, 2019·Neurochemical Research·Monica ArmidaRosa Luisa Potenza
Aug 29, 2019·Frontiers in Cellular Neuroscience·Jonu PradhanMark C Bellingham
Apr 26, 2018·Frontiers in Pharmacology·Ágatha Oliveira-GiacomelliHenning Ulrich
Nov 9, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Catarina Miranda-LourençoMaria J Diógenes
Apr 17, 2021·Cellular Reprogramming·Muhmmad AtifQaisar Raza
Jun 1, 2021·Frontiers in Pharmacology·Mercedes Garcia-GilMaria Grazia Tozzi
Jun 1, 2021·Frontiers in Neurology·Marie J PietrowskiKevin Carvalho
Aug 3, 2021·Frontiers in Neuroscience·Ana Moreira-de-SáRodrigo A Cunha

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