S62 lymphocytes, epithelial cells from various tissues, and in the GI smooth muscle [1]. As new roles for these receptors are continuously being unraveled and being that most pharmacological tools available to study these receptors are far from specific and mutually affect various receptors, the use of specific antibodies has become essential to study them. Alomone Labs offers specific polyclonal antibodies targeted against all P2Y receptors, enabling the end user to specifically detect the identity of the receptor in question. We would like to emphasize that the use of antibodies is by no means a replacement, but should be used in concert with the pharmacological tools available. This short communi- cation illustrates the purpose and the many advantages using antibodies, specifically Alomone Labs antibodies, have in researching purinergic signaling. P2Y receptors in the CNS Although extracellular purines may have both trophic and apoptotic functions in the brain depending on the targeted purine receptor and cell type, little is known about the role of specific purine receptors in neurons [2]. It was shown that both ADP and its stable analogue 2-methylthio-ADP (2MeSADP) induced the upregulation of the cytoprotective protein heme oxygenase-1 in rat cerebellar granule neurons. Selective inhibition of 2MeSADP-responsive receptors P2Y1 and P2Y13 and the use of pertussis toxin demonstrat- ed a role of the purinergic P2Y13 receptor in this response. Western blot analysis using anti-P2Y1 receptor (#APR-017) and anti-P2Y13 receptor (#APR-017) antibodies confirmed those results. These observations reveal a previously unrecognized role in protection against oxidative stress by extracellular purines acting on the metabotropic P2Y13 receptor and provide new perspectives for neuroprotective therapies. Microglial cells are the primary immune effector cells in the brain. Extracellular ATP, e.g., released after brain injury, may initiate microglial activation via the stimulation of purinergic receptors. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of lower and upper motoneurons. The pathology is imputable in ∼2% of cases to mutations in the ubiquitous enzyme Cu,Zn superoxide dismutase (SOD1). Common theories to explain the pathogenic mechanisms of ALS include the activation of the microglia, responsible for the release of pro-inflammatory factors. The effect of mutant SOD1 on P2 receptor-mediated pro-inflammatory microglial properties was investigated [3]. Primary and immortalized microglial cells from mutant SOD1 mice were used to explore several aspects of activation by purinergic ligands and to analyze the overall effect of such stimulation on the viability of NSC-34 and SH-SY5Y neuronal cell Purinergic Signalling (2012) 8 (Suppl 1):S61–S79 lines. The upregulation of P2Y6 receptors (without changes in P2Y2 and P2Y12 receptors) and the downregulation of ATP-hydrolyzing activities in mutant SOD1 microglia were observed using anti-P2Y6 receptor (#APR-006), anti-P2Y2 receptor (#APR-010), and anti-P2Y12 receptor antibodies in Western blot analysis. The purinergic activation of the microglia may thus constitute a new route involved in the progression of ALS to be exploited to potentially halt the disease. The uridine nucleotide-activated P2Y2, P2Y4, and P2Y6 receptors are widely expressed in the brain and are involved in many CNS processes, including those which malfunction in Alzheimer’s disease (AD). However, the status of these receptors in the AD neocortex, as well as their putative roles in the pathogenesis of neuritic plaques and neurofi- brillary tangles, remain unclear. In this study, Lai et al. [4] used immunoblotting and immunohistochemistry using anti-P2Y2 receptor, anti-P2Y4 receptor (#APR-006), and anti-P2Y6 receptor antibodies in order to measure P2Y2, P2Y4, and P2Y6 receptors, respectively, in two regions of the postmortem neocortex of AD patients and aged controls. P2Y2 immunoreactivity was found to be selec- tively reduced in the AD parietal cortex, while P2Y4 and P2Y6 levels were unchanged. In contrast, all three receptors were preserved in the occipital cortex, which is known to be minimally affected by AD neuropathology. Furthermore, reductions in parietal P2Y2 immunoreactivity correlated both with neuropathologic scores and markers of synapse loss. These results provide a basis for considering P2Y2 receptor changes as a neurochemical substrate of AD and point toward uridine nucleotide-activated P2Y receptors as novel targets for disease-modifying AD pharmacotherapeu- tic strategies. In the CNS, P2 receptors are identified in neurons and glial cells, mediating neuron–neuron, glia–glia, and glia– neuron communication. Amadio et al. [5] qualified in vivo in the adult rat CNS the cellular/subcellular distribution of P2Y12 receptor in the cerebral cortex, white matter, and subcortical nuclei (striatum and substantia nigra) by means of electron microscopy, immunofluorescence, confocal, and Western blot analysis using anti-P2Y12 receptor (#APR- 012) antibody. P2Y12 receptor immunoreactivity co- localized only with myelin basic protein and the oligoden- drocyte marker RIP in both cell bodies and processes, indicating therefore oligodendrocyte localization. Since in platelets the P2Y12 receptor is known to regulate adhesion/ activation and thrombus growth/stability, results from the study presented helped speculate by analogy that, in oligodendrocytes, P2Y12 receptor signaling might contrib- ute to the migration and adhesion of the glial processes to axons to be myelinated. Apolloni et al. [6] established the direct toxic role and anticancer activity of UDP in a neuroblastoma cell line SH-