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Impact of adenosine signaling on mutant LRRK2 induced neuronal injury
Author(s) -
Steer Erin,
Chu Charleen
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1035.10
Subject(s) - adenosine , ccpa , adenosine receptor , agonist , pharmacology , adenosine a1 receptor , neurite , astrogliosis , adenosine a2b receptor , adenosine kinase , chemistry , receptor , biology , microbiology and biotechnology , endocrinology , biochemistry , adenosine deaminase , central nervous system , in vitro
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 A 1 adenosine receptors (A 1 AR) and blockade of the A 2 adenosine receptors (A 2A AR) 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 A 1 AR agonist [2‐chloro‐N6‐cyclopentyladenosine (CCPA)], or a selective A 2A AR 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.