Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation.

Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation. Annu Rev Pharmacol Toxicol. 2018 Sep 12;: Authors: Moutinho M, Codocedo JF, Puntambekar SS, Landreth GE Abstract Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreview...
Source: Annual Review of Pharmacology and Toxicology - Category: Drugs & Pharmacology Authors: Tags: Annu Rev Pharmacol Toxicol Source Type: research