Lewandowski and colleagues report that 22q11 deletion...
Lewandowski and colleagues report that 22q11 deletion syndrome participants exhibited deficits in intelligence, achievement, sustained attention, executive functioning, and verbal working memory compared to controls. It's interesting that eczema and asthma are seen in chromosome 22q11.2 deletion syndrome (Staple et al., 2005). The adenosine A2A receptor is found at 22q11.2 and deficient A2A receptor activity leads to airway inflammation in an asthma model (Nadeem et al., 2007). This would seem to indicate increased A2B receptor activity as a consequence.
A patent issued on October 24, 2006 (http://www.patentgenius.com/patent/7125993.html), describes an A2B adenosine receptor antagonist for the treatment of type I hypersensitivity disorders, such as asthma, hay fever, and atopic eczema. They also state, "Another adverse biological effect of adenosine acting at the A.sub.2B receptor is the overstimulation of cerebral IL-6, a cytokine associated with dementias and Alzheimer's disease. Inhibiting the binding of adenosine to A.sub.2B receptors would therefore mitigate those neurological disorders that are produced by IL-6." Carta et al. (Carta et al., 2002) find a correlation between the degree of mental retardation and IL-6 in patients with Down syndrome. I wonder whether there might also be a similar correlation in those with 22q11.2 deletions. Perhaps an A2B adenosine receptor antagonist may help alleviate the deficits in intelligence as well as the hypersensitivity disorders associated with this condition.
It's interesting that adenosine signaling by the A2B receptor might stimulate hair growth through FGF-7 upregulation in dermal papilla cells as abundant scalp hair has been reported in DiGeorge chromosome region deletions (Ravnan et al., 1996; Iino et al., 2007). Deletions at 22q11 have also been associated with autosomal-dominant polycystic kidney disease in which increased FGF-7 expression is reported (Gogusev et al., 2003; Mei et al., 2005). Perhaps the A2A adenosine receptor may be a candidate.
In view of the association with 22q11 deletions and the increased risk of schizophrenia, it's also of interest that translin-associated protein X (TRAX) has been found to interact with the A2A adenosine receptor. The DISC1/TRAX locus has been implicated in schizophrenia in several studies (Sun et al., 2006; Cannon et al., 2005).
Further evidence to support a role for the A2A adenosine receptor in the development of schizophrenia is that it is known to regulate cyclic AMP levels. DISC1 interacts with phosphodiesterase (PDE) 4B that degrades cyclic AMP. Depression, mania, schizophrenia, paranoia, anxiety, and obsessive and obsessive compulsive disorders are reported in patients with Huntington's disease (Barquero-Jimenez et al., 2001), while Tarditi and colleagues (Tarditi et al., 2006) suggest that alteration of A2A receptor signaling is present in HD. Wang et al. (Wang et al., 2003) report reduced prepulse inhibition and startle habituation in mice lacking the A2A adenosine receptor.