Editorial [Hot Topic: Cyclooxygenases and Cyclooxygenase Inhibitors in Neurological and Psychiatric Diseases (Executive Editor: Luisa Minghetti) ]

In the last decade, the potential role of cyclooxygenase (COX) activity in brain diseases has been extensively studied. In particular, the association between the COX-2 isoform and neurotoxic processes has been proposed for several neurological conditions, including acute and chronic diseases. The beneficial effects of COX inhibitors observed in several experimental models and in retrospective epidemiological studies have further, albeit indirectly, supported COX-2 as a major therapeutic target to treat brain diseases. Nonetheless, the role played by each COX isoform in neurodegenerative diseases is still controversial and the emerging role of COX-2 in behavioural and cognitive functions strongly indicates that studies aimed at improving our knowledge of physiological role of COX-2 in the central nervous system are crucial to fully understand the pros and cons of COX-2 manipulation in disabling neurological and psychiatric diseases. The purpose of this issue of Current Pharmaceutical Design is to provide a comprehensive overview of the role of COX activity in the pathogenesis of neurodegenerative diseases and therapeutic potential of its inhibition. In addition, the issue is intended to highlight novel aspects of the physiological and pathological function of COXs, and particularly of the COX-2 isoform. The first three articles concern three major neurological conditions, such as cerebral ischemia, Alzheimer's disease (AD) and Parkinson's disease (PD). Candelario-Jalil and Fiebich [1], review current knowledge of the relative contribution of COX isoforms to the brain ischemic pathology and offer a critical evaluation of the therapeutic potential of COX inhibitors in cerebral ischemia, highlighting the new targets identified downstream of COX with potential neuroprotective ability. Hoozemans and colleagues [2], provide a critical overview of the controversial role of COX isoforms in the pathogenesis of AD. The authors discuss of the diverse roles of COX-1 and COX-2 in the different stages of AD pathology and their involvement in inflammatory and regenerating pathways. Asanuma and Miyazaki [3] emphasize the heterogeneous pharmacological properties of non steroidal anti-inflammatory drugs (NSAIDs), which are likely to contribute to the protection of dopaminergic neurons in number of experimental studies using parkinsonian models, and discuss the discrepancy of effects of NSAIDs in experimental and epidemiological studies. The fourth article focuses on the recent interest in anti-inflammatory treatments as tools to foster endogenous neurogenesis in the attempt to re-establish the lost tissue integrity in major brain diseases. Ajmone-Cat and colleagues [4] point out the complexity of inflammation and glial responses to acute or chronic injuries and the likelihood to generate either harmful or beneficial effects by interfering with them through NSAID treatment. The last two articles cover the recent advancements on the role of COX-2 in neurotransmission and psychiatric disturbances. Yang and Chen [5] discuss the involvement of COX-2 activity in excitatory glutamatergic and long-term potentiation (LTP) and the recent evidence proving that endogenous cannabinoids are substrates for COX-2 and precursors of new classes of prostaglandins that could modulate synaptic transmission and plasticity. Mueller and Schwarz [6] report on the recent involvement COX-2 and prostaglandin E2 in the immunological imbalance observed in schizophrenia and in depression and on the experimental and clinical evidence supporting beneficial effects of antiinflammatory therapies in these psychiatric disorders. Finally, as an Executive Editor of Current Pharmaceutical Design, I would like to thank all the authors contributing to this issue, for their time and effort. References [1] Candelario-Jalil E, Fiebich BL. Cyclooxygenase inhibition in ischemic brain injury. Curr Pharm Des 2008; 1414): 1401-1418. [2] Hoozemans JJ, Rozemuller JM, van Haastert ES, Veerhuis R, Eikelenboom P. Cyclooxygenase -1 and 2 in the different stages Alzheimer's disease pathology. Curr Pharm Des 2008; 14(14): 1419-1427.