ER stress and neurodegenerative diseases.
Endoplasmic reticulum (ER) stress is caused by disturbances in the structure and function of the ER with the accumulation of misfolded proteins and alterations in the calcium homeostasis. The ER response is characterized by changes in specific proteins, causing translational attenuation, induction of ER chaperones and degradation of misfolded proteins. In case of prolonged or aggravated ER stress, cellular signals leading to cell death are activated. ER stress has been suggested to be involved in some human neuronal diseases, such as Parkinson's disease, Alzheimer's and prion disease, as well as other disorders. The exact contributions to and casual effects of ER stress in the various disease processes, however, are not known. Here we will discuss the possible role of ER stress in neurodegenerative diseases, and highlight current knowledge in this field that may reveal novel insight into disease mechanisms and help to design better therapies for these disorders.
Lindholm
D
D
Department of Neuroscience, Unit of Neurobiology, Uppsala University, Biomedical Centre, Box 587, S-751 23 Uppsala, Sweden. dan.lindholm@neuro.uu.se
Wootz
H
H
Korhonen
L
L
D000544:Alzheimer Disease / Q000209:etiology; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology*; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology; D017096:Prion Diseases / Q000209:etiology; D017510:Protein Folding