The need for newer compounds to treat depression is an ever-growing concern due to the enormous societal and financial ramifications of this disorder. Here, we review some of the candidate systems that could potentially be involved in depression, or an inherent resistance to depression termed resilience, and the numerous protein targets for these systems. A substantial body of literature provides strong evidence that neurotrophic factors, glutamate receptors, hypothalamic feeding peptides, nuclear hormone receptors, and epigenetic mechanisms, among others, will make for interesting targets when examining depressive behavior or resilience in preclinical models, and eventually clinical trials. Although some of these targets for depression already appear promising, new waves of more selective compounds for any molecular system should promote a better understanding of this complex disease and perhaps improved treatments.
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