Редактирование: ADORA2B

Adenosine receptor A2b

==Publications==

{{medline-entry
|title=Adenosine A2B receptor: A pathogenic factor and a therapeutic target for sensorineural hearing loss.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33131093
|abstract=Over 466 million people worldwide are diagnosed with hearing loss (HL). About 90% of HL cases are sensorineural HL (SNHL) with treatments limited to hearing aids and cochlear implants with no FDA-approved drugs. Intriguingly, [[ADA]]-deficient patients have been reported to have bilateral SNHL, however, its underlying cellular and molecular basis remain unknown. We report that Ada  mice, phenocopying [[ADA]]-deficient humans, displayed SNHL. Ada  mice cochlea with elevated adenosine caused substantial nerve fiber demyelination and mild hair cell loss. [[ADA]] enzyme therapy in these mice normalized cochlear adenosine levels, attenuated SNHL, and prevented demyelination. Additionally, [[ADA]] enzyme therapy rescued SNHL by restoring nerve fiber structure in Ada  mice post two-week drug withdrawal. Moreover, elevated cochlear adenosine in untreated mice was associated with enhanced Adora2b gene expression. Preclinically, [[ADORA2B]]-specific antagonist treatment in Ada  mice significantly improved HL, nerve fiber density, and myelin compaction. We also provided genetic evidence that [[ADORA2B]] is detrimental for age-related SNHL by impairing cochlear myelination in WT aged mice. Overall, understanding purinergic molecular signaling in SNHL in Ada  mice allows us to further discover that [[ADORA2B]] is also a pathogenic factor underlying aged-related SNHL by impairing cochlear myelination and lowering cochlear adenosine levels or blocking [[ADORA2B]] signaling are effective therapies for SNHL.

|keywords=* ADA-deficiency
* adenosine deaminase deficiency
* aging
* myelin protein zero
* myelination
|full-text-url=https://sci-hub.do/10.1096/fj.202000939R
}}