title: Translating protein phosphatase research into treatments for neurodegenerative diseases.
abstract: Many of the major neurodegenerative disorders are characterized by the accumulation of intracellular protein aggregates in neurons and other cells in brain, suggesting that errors in protein quality control mechanisms associated with the aging process play a critical role in the onset and progression of disease. The increased understanding of the unfolded protein response (UPR) signaling network and, more specifically, the structure and function of eIF2α phosphatases has enabled the development or discovery of small molecule inhibitors that show great promise in restoring protein homeostasis and ameliorating neuronal damage and death. While this review focuses attention on one or more eIF2α phosphatases, the wide range of UPR proteins that are currently being explored as potential drug targets bodes well for the successful future development of therapies to preserve neuronal function and treat neurodegenerative disease.
authors.affiliation: Signature Programs in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore.
authors.forename: Jeyapriya R
authors.initials: JR
authors.lastname: Sundaram
authors.affiliation: Signature Programs in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore.
authors.forename: Irene C J
authors.initials: IC
authors.lastname: Lee
authors.affiliation: Signature Programs in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore shirish.shenolikar@duke-nus.edu.sg.|Signature Programs in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore.
authors.forename: Shirish
authors.initials: S
authors.lastname: Shenolikar
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical / Q000379:methods*; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D010749:Phosphoprotein Phosphatases
keywords: neurodegeneration; protein phosphatases; therapeutics; translation factors; unfolded protein response