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The participation of silent mating type information regulation 2 homolog 1 (SIRT1) in amyotrophic lateral sclerosis (ALS) has been reported in many studies. However, the role of the expression and function of SIRT1 in the hypothalamus in ALS remains unknown. In the current study, we performed western blot, co-immunoprecipitation and immunofluorescence analyses to determine the expression and in-depth mechanism of SIRT1 in the hypothalamus in SOD1G93A transgenic mice. We found that SIRT1 was overexpressed in the hypothalamus after motor symptom onset. In addition, SIRT1 interacted with prepro-orexin, a molecule involved in energy balance and the sleep/wake cycle, in both preclinical and clinical ALS regardless of whether SIRT1 levels were elevated. These findings indicate that SIRT1 might participate in sleep and metabolic changes in ALS, suggesting that SIRT1 is a new target for ALS treatment. [ABSTRACT FROM AUTHOR]

To know the processes involved in feeding, the dysregulation of hypothalamic neuropeptides promoting anorexigenic/orexigenic mechanisms must be investigated. Many neuropeptides are involved in this behavior and in overweight/obesity. Current pharmacological strategies for the treatment of obesity are unfortunately not very effective and, hence, new therapeutic strategies must be investigated and developed. Due to the crucial role played by orexins in feeding behavior, the aim of this review is to update the involvement of the orexinergic system in this behavior. The studies performed in experimental animal models and humans and the relationships between the orexinergic system and other substances are mentioned and discussed. Promising research lines on the orexinergic system are highlighted (signaling pathways, heterogeneity of the hypothalamic orexinergic neurons, receptor-receptor interaction, and sex differences). Each of the orexin 1 and 2 receptors plays a unique role in energy metabolism, exerting a differential function in obesity. Additional preclinical/clinical studies must be carried out to demonstrate the beneficial effects mediated by orexin receptor antagonists. Because therapies applied are in general ineffective when they are directed against a single target, the best option for successful anti-obesity treatments is the development of combination therapies as well as the development of new and more specific orexin receptor antagonists. [ABSTRACT FROM AUTHOR]