Current medicinal chemistry
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Although the pathophysiological mechanisms underlying the development of amyotrophic lateral sclerosis (ALS) remain to be fully elucidated, there have been significant advances in the understanding of ALS pathogenesis, with evidence emerging of a complex interaction between genetic factors and dysfunction of vital molecular pathways. Glutamate- mediated excitoxicity is an important pathophysiological pathway in ALS, and was identified as an important therapeutic biomarker leading to development of the only pharmacologically based disease-modifying treatment currently available for ALS. ⋯ Genetic therapies, including antisense oligonucleotide approaches have been shown to exert neuroprotective effects in animal models of ALS, and Phase I human trial have been completed demonstrating the feasibility of such a therapeutic approach. The present review summarises the advances in ALS pathogenesis, emphasising the importance of these processes as potential targets for drug development in ALS.
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Indocyanine green (ICG) is a water-soluble anionic tricarbocyanine dye developed during the Second World War that was first approved for clinical use in humans in 1956. The main features of ICG that make it suitable for bioimaging applications are its near infrared absorption and its fluorescence. ⋯ Moreover, ICG can be used for hyperthermia of enhanced-photocoagulation of blood vessels treatment. In this paper we have gathered all the available data concerning the use of ICG for different treatments.
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Voltage-gated sodium channels are large transmembrane protein complexes responsible for the propagation and transmission of electrical impulses through nerve, muscle and endocrine cells and cell systems. Dysregulated expression and/or functional changes of ion channel isoforms are found in many associated pathological conditions. In such cases, modulation of voltage gated sodium channels (Na(V) channels) is a recognised approach in medicinal chemistry. ⋯ Such compounds offer selective targeting and new possibilities for studying the physiology of Na(V) channels and pathophysiology of the associated ailment conditions. This review consolidates the recent literature on Na(V) 1.3, 1.7 and 1.8 channel isoform selective and/or state-dependent modulators. In particular, their structure-activity relationship is illustrated, especially in the context of selectivity on a particular isoform, and their applicability in the therapy of neuropathic pain is described.