A(2A) adenosine receptors are up-regulated in lymphocytes from amyotrophic lateral sclerosis patients

作者：Vincenzi Fabrizio; Corciulo Carmen; Targa Martina; Casetta Ilaria; Gentile Mauro; Granieri Enrico; Borea Pier Andrea; Popoli Patrizia; Varani Katia^*

来源：Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2013, 14(5-6): 406-413.

DOI：10.3109/21678421.2013.793358

• Adenosine receptors
• ALS patients
• human lymphocytes
• saturation binding experiments
• cyclic AMP assays

Adenosine, a purine nucleoside interacting with A 1, A(2A), A(2B) and A(3) adenosine receptors (ARs), is a potent endogenous modulator of inflammatory and neuronal processes involved in the pathophysiology of several neurodegenerative diseases. In the present study, ARs were investigated in lymphocytes from patients with amyotrophic lateral sclerosis (ALS) and compared with age-matched healthy subjects. In ALS patients A(2A)ARs were analysed by using RT-PCR, Western blotting and saturation binding experiments. The effect of A(2A)AR stimulation on cyclic AMP levels was evaluated in lymphocytes from ALS patients and healthy subjects. %26lt;br%26gt;An up-regulation of A(2A)ARs was observed in ALS patients with respect to healthy subjects while A(1), A(2B) and A(3)AR affinity and density did not change. In ALS patients, the A(2A)AR density values correlated with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Furthermore, the stimulation of A(2A)ARs mediated a significant increase in cyclic AMP levels in lymphocytes from ALS patients, with a higher potency than in lymphocytes from healthy subjects. In conclusion, the positive correlation between A(2A)AR density and ALSFRS-R scores could indicate a possible protective effect of this receptor subtype, representing an interesting starting point for the study of alternative therapeutic approaches for ALS based on A(2A)AR modulation.

• 出版日期2013-9