P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy - Archive ouverte HAL Access content directly
Journal Articles PLoS Medicine Year : 2015

P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy

, , , (1) , , , , , (2) , , (3) , , , , (4) , , , ,
1
2
3
4
Anthony Sinadinos
  • Function : Author
Christopher Young
  • Function : Author
Rasha Al-Khalidi
  • Function : Author
Paweł Kalinski
  • Function : Author
Shafini Mohamad
  • Function : Author
Léonore Floriot
  • Function : Author
Tiphaine Henry
  • Function : Author
Taiwen Jiang
  • Function : Author
Alexis Lefebvre
  • Function : Author
Mikhail Shugay
  • Function : Author
Jie Tong
  • Function : Author
Stephen Arkle
  • Function : Author
Jean-Claude Dorego
  • Function : Author
Dariusz Górecki
Gary Peltz
  • Function : Author

Abstract

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP-P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target.

Dates and versions

hal-02058099 , version 1 (05-03-2019)

Identifiers

Cite

Anthony Sinadinos, Christopher Young, Rasha Al-Khalidi, Anna Teti, Paweł Kalinski, et al.. P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy. PLoS Medicine, 2015, 12 (10), pp.e1001888. ⟨10.1371/journal.pmed.1001888⟩. ⟨hal-02058099⟩
41 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More