Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders |
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Authors: | Doyle Karen M Kennedy Donna Gorman Adrienne M Gupta Sanjeev Healy Sandra J M Samali Afshin |
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Affiliation: | School of Medicine, NUI Galway, Galway, Ireland. |
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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. |
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Keywords: | neurodegeneration ER stress UPR apoptosis autophagy Alzheimer’s disease Parkinson’s disease amyotrophic lateral sclerosis prions disease |
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