Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation.
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.
['Moutinho|Miguel|M|', 'Codocedo|Juan F|JF|', 'Puntambekar|Shweta S|SS|', 'Landreth|Gary E|GE|']
D000818:Animals D001921:Brain D006801:Humans D019636:Neurodegenerative Diseases D009474:Neurons D018160:Receptors, Cytoplasmic and Nuclear D059467:Transcriptome
nuclear receptors neurodegenerative diseases Alzheimer's disease Huntington's disease Parkinson's disease amyotrophic lateral sclerosis