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Nephi Stella"Identifying new components of endocannabinoid signaling: involvement in neuroinflammation"

Abstract :

My laboratory is interested in identifying the molecular machinery controlling pathology-induced changes in glial cell phenotype,
with the aim of developing pharmacological tools that will minimize the harmful phenotype of glial cells and reinstate – or even boost – their reparative function. Our current most promising target is the cannabinoid signaling system. Cannabinoids, the bioactive components produced by the marijuana plant Cannabis Sativa, have immunomodulatory properties that are quite different from currently available immunomodulatory drugs. They act through specific receptors named CB1 and CB2. CB1 receptors are expressed by neurons and mediate the drug of abuse properties of marijuana, while CB2 receptors are expressed by immune and glial cells and mediate its immunomodulatory properties. This dichotomy has tremendous therapeutic potential for it allows the development of agents that specifically target CB2 receptors and thus regulate immune functions without inducing the drug of abuse adverse effects mediated through CB1 receptors. Cannabinoid receptors are normally activated by endogenous ligands, the endocannabinoids.
We are currently testing the hypothesis that agents acting through CB2 receptors or blocking the degradation of endocannabinoids can modulate the detrimental neuroinflammatory responses occurring as a result of brain ischemia and multiple sclerosis. We chose to study these pathologies because they remain without cure and thus demand regimented scientific efforts to relieve these patients. We are also using novel genetic and proteomics approaches to identify novel cannabinoid receptors and enzymes degrading endocannabinoids, with the hope that these proteins can also be targeted for therapy. Our goal is to identify cannabinoid-based targets and agents devoid of drug of abuse pro

Selected publications

Mackie K, Stella N. Related Articles,
Cannabinoid receptors and endocannabinoids: evidence for new players.
AAPS J. 2006 Apr 28;8(2):E298-306. Review.

Manning HC, Smith SM, Sexton M, Haviland S, Bai M, Cederquist K, Stella N, Bornhop DJ.
A peripheral benzodiazepine receptor targeted agent for in vitro imaging and screening.
Bioconjug Chem. 2006 May-Jun;17(3):735-40.
Witting A, Chen L, Cudaback E, Straiker A, Walter L, Rickman B, Moller T, Brosnan C, Stella N.
Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection.
Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6362-7. Epub 2006 Mar 29.
Aguado T, Palazuelos J, Monory K, Stella N, Cravatt B, Lutz B, Marsicano G, Kokaia Z, Guzman M, Galve-Roperh I.
The endocannabinoid system promotes astroglial differentiation by acting on neural progenitor cells.
J Neurosci. 2006 Feb 1;26(5):1551-61.

Giovanni Marsicano