Editorial [Hot topic: Endocannabinoid Signaling and Neuroinflammatory Diseases (Executive Editor: Mauro Maccarrone)]

E-ISSN： 1873-4286|14|23|2252-2253

ISSN： 1381-6128

Source： Current Pharmaceutical Design, Vol.14, Iss.23, 2008-08, pp. : 2252-2253

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Abstract

Endocannabinoids are endogenous agonists of cannabinoid receptors, and comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the best-studied members of this new class of lipid mediators [1]. It is now widely accepted that the in vivo concentration and biological activity of endocannabinoids are largely dependent on a “metabolic control”. Therefore, the proteins that synthesize, transport and degrade endocannabinoids, and that together with the target receptors form the so-called “endocannabinoid system (ECS)”, are the focus of intense research. This new system will be presented in this Hot Topic issue of Current Pharmaceutical Design, in order to put in a better perspective the role of endocannabinoid signaling in the immune surveillance of the central nervous system (CNS) [2], and in the control of neuronal [3] and glial [4] cell survival and death. The impact of ECS on neuroinflammatory diseases like Alzheimer's disease (AD) [5], amyotrophic lateral sclerosis (ALS) [6], Huntington's disease (HD) [7], multiple sclerosis (MS) [8], and Parkinson's disease (PD) [9], as well as in pathological conditions like ischemia/ repurfusion injury [10] and encephalopathia [11], will be also presented in detail in specific chapters, contributed by leading scientists in the field. In addition, the pharmacology of synthetic and plant-derived agonists and antagonists of endocannabinoid receptors, or of inhibitors of endocannabinoid metabolism [12], will be discussed in the context of their potential exploitation as therapeutics, able to delay or arrest the onset and/or progression of neuroinflammatory disorders. Finally, ECS alterations in blood cells that mirror CNS dysfunctions, and thus might be exploited as diagnostic markers or therapeutic targets of neuroinflammatory diseases, will be reviewed [13].It should be recalled that the classical distinction between degenerative and inflammatory disorders of the CNS is vanishing, because growing evidence demonstrates that inflammatory processes are important in the pathophysiology of primarily degenerative disorders, and conversely neurodegeneration complicates primarily inflammatory diseases of the brain and spinal cord. In particular, evidence has been accumulated to suggest that these two processes coexist from the very early stages of both classical neurodegenerative disorders and classical inflammatory diseases of the CNS. As a matter of fact, recognition of the inflammatory reaction accompanying neurodegeneration, and of the neurodegeneration accompanying inflammation, is not unprecedented. For example, activation of microglia and of astrocytes, which are part of the innate immune system in the CNS, has been identified as a cardinal feature of AD pathology in the brain. Similarly, neuronal injury has been known to be involved in MS since the first description of the disease by Charcot (reviewed in ref. [14]). Yet, such findings did not attract much attention in the past, because reactive gliosis was considered only an unspecific, scar-like response to neuronal death during degenerative damage, and neuronal loss was thought to be a late consequence of axon demyelination in MS. Later discoveries have imposed reconsideration of the perceived relationship between inflammation and neurodegeneration, and common molecular pathways that bring these two processes together have been described [15, 16]. Also the capacity of activated immune cells to damage neurons in the absence of any antigen specificity [17, 18], and the ability of damaged neurons to trigger local immune responses [19], has been clearly demonstrated. Recently, the contribution of degenerative and inflammatory processes to CNS disorders such as AD, ALS, PD, MS and HIV-associated dementia has been extensively reviewed [20]. It should be highlighted that AD, ALS and PD are among the best examples of neurodegenerative disorders associated wi