Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders
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2011-09-26Author
Doyle, Karen M.
Kennedy, Donna
Gorman, Adrienne M.
Gupta, Sanjeev
Healy, Sandra J. M.
Samali, Afshin
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Doyle, Karen M. Kennedy, Donna; Gorman, Adrienne M.; Gupta, Sanjeev; Healy, Sandra J. M.; Samali, Afshin (2011). Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders. Journal of Cellular and Molecular Medicine 15 (10), 2025-2039
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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 Ca2+-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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