title: Unfolding the promise of translational targeting in neurodegenerative disease.
abstract: With the rise of aging populations, new challenges for health care systems are emerging. Degenerative conditions of the central nervous system share a strikingly great deal of similarities, particularly the production and buildup of malfolded proteins. As a result, stress pathways within the endoplasmic reticulum become activated, triggering widespread neuronal apoptosis. New pharmacological compounds targeting this response are emerging as promising treatment strategies. This review examines the current evidence for protein aggregation in neurodegenerative disease states and discusses future mechanisms of therapeutically targeting the endoplasmic reticulum.
authors.affiliation: Academic Unit of Surgical Oncology, The Medical School, University of Sheffield, Sheffield, S10 2RX, UK, tmdrake1@sheffield.ac.uk.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Drake
mesh_terms: D051702:Activating Transcription Factor 6 / Q000502:physiology; D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D060833:Cellular Microenvironment / Q000187:drug effects; D003620:Dantrolene / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004722:Endoribonucleases / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D018832:Molecular Chaperones / Q000502:physiology; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017510:Protein Folding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D056811:Unfolded Protein Response / Q000187:drug effects*; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D051702:Activating Transcription Factor 6; D003620:Dantrolene; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016859:Lipoxygenase Inhibitors; D008911:Minocycline; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C528229:ERN1 protein, human