Impact of adenosine signaling on mutant LRRK2 induced neuronal injury

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, affecting more than 1.5% of people over the age of 65. The most common genetic cause of PD is mutations in the gene for leucine‐rich repeat kinase 2 (LRRK2). Consumption of caffeine, a non‐selective adenosine receptor antagonist, has been linked to decreased incidence of PD. Additionally, activation of A1 adenosine receptors (A1AR) and blockade of the A2 adenosine receptors (A2AAR) have been shown to protect neurons against pathogenic stimuli. Therefore, we hypothesized that manipulation of the adenosine signaling pathway would attenuate mutant LRRK2 induced neurite retraction and cell death. Number of neuritic branch points and neurite length were measured in mouse cortical neurons expressing LRRK2 mutants following treatment with adenosine, a selective A1AR agonist [2‐chloro‐N6‐cyclopentyladenosine (CCPA)], or a selective A2AAR antagonist [7‐(2‐phenylethyl)‐5‐amino‐2‐(2‐furyl)‐pyrazolo‐[4,3‐e]‐1,2, 4‐triazolo[1,5‐c]pyrimidine (SCH 58261)].These data will indicate if adenosine signaling is able to protect against neurite retraction induced by mutant LRRK2.