The Role of ER Stress-Induced Apoptosis in Neurodegeneration
Ioanna C. Stefani, Daniel Wright, Karen M. Polizzi and Cleo Kontoravdi
Affiliation: Department of Chemical Engineering, Imperial College London, London SW7 2AZ, U.K.
Keywords: Apoptosis, calcium dyshomeostasis, endoplasmic reticulum stress, neurodegeneration, oxidative stress, reactive
Post-mortem analyses of human brain tissue samples from patients suffering from neurodegenerative disorders
have demonstrated dysfunction of the endoplasmic reticulum (ER). A common characteristic of the aforementioned disorders
is the intracellular accumulation and aggregation of proteins due to genetic mutations or exogenous factors, leading to
the activation of a stress mechanism known as the unfolded protein response (UPR). This mechanism aims to restore cellular
homeostasis, however, if prolonged, can trigger pro-apoptotic signals, which are thought to contribute to neuronal
cell death. The authors present evidence to support the role of ER stress-induced apoptosis in Alzheimer’s, Parkinson’s
and Huntington’s diseases, and further examine the interplay between ER dyshomeostasis and mitochondrial dysfunction,
and the function of reactive oxygen species (ROS) and calcium ions (Ca2+) in the intricate relationship between the two
organelles. Possible treatments for neurodegenerative diseases that are based on combating ER stress are finally presented.
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