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  • Title: [Neurodegenerative, autoimmune and genetic processes of human and animal narcolepsy].
    Author: Dauvilliers Y.
    Journal: Rev Neurol (Paris); 2003 Nov; 159(11 Suppl):6S83-7. PubMed ID: 14646805.
    Abstract:
    Narcolepsy is a rare disabling sleep disorder whose main features are excessive daytime sleepiness and cataplexy. Human narcolepsy is most frequently a sporadic disorder with both genetic and environmental factors playing a role in its pathophysiology. Implication of the hypocretin system is well-established: as mutations in both canine and murine narcolepsies and as a consistent reduction in hypocretin neuron in human narcolepsy. The cause of human narcolepsy remains unknown. However degenerative, autoimmune and/or genetic processes are the most probable causes of the hypocretin neurons loss. Acting on a specific genetic background, an autoimmune process with hypocretin neuron degeneration, in response to environmental factors, is the most probable hypothesis for most cases of human narcolepsy with cataplexy. Although narcolepsy presents one of the tightest association with a specific HLA antigen (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility. Monoaminergic, immune (TNF alpha) and hypocretinergic systems seem to be involved and may interfere with the phenotype. Treatment has not evolved significantly over the last few years. However, new drugs, such as hypocretin agonists, are currently being developed.
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