title: Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders.
abstract: The stimuli for neuronal cell death in neurodegenerative disorders are multi-factorial and may include genetic predisposition, environmental factors, cellular stressors such as oxidative stress and free radical production, bioenergy failure, glutamate-induced excitotoxicity, neuroinflammation, disruption of Ca(2+) -regulating systems, mitochondrial dysfunction and misfolded protein accumulation. Cellular stress disrupts functioning of the endoplasmic reticulum (ER), a critical organelle for protein quality control, leading to induction of the unfolded protein response (UPR). ER stress may contribute to neurodegeneration in a range of neurodegenerative disorders. This review summarizes the molecular events occurring during ER stress and the unfolded protein response and it specifically evaluates the evidence suggesting the ER stress response plays a role in neurodegenerative disorders.
authors: School of Medicine, NUI Galway, Galway, Ireland.
authors: Karen M
authors: KM
authors: Doyle
authors: Donna
authors: D
authors: Kennedy
authors: Adrienne M
authors: AM
authors: Gorman
authors: Sanjeev
authors: S
authors: Gupta
authors: Sandra J M
authors: SJ
authors: Healy
authors: Afshin
authors: A
authors: Samali
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001343:Autophagy / Q000235:genetics; D059865:Endoplasmic Reticulum Stress; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D004722:Endoribonucleases; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C497111:ATF6 protein, human; C403982:ERN2 protein, human