TAILIEUCHUNG - Báo cáo khoa học: ER stress and diseases

Proteins synthesized in the endoplasmic reticulum (ER) are properly folded with the assistance of ER chaperones. Malfolded proteins are disposed of by ER-associated protein degradation (ERAD). When the amount of unfolded protein exceeds the folding capacity of the ER, human cells acti-vate a defense mechanism called the ER stress response, which induces expression of ER chaperones and ERAD components and transiently attenuates protein synthesis to decrease the burden on the ER. | REVIEW ARTICLE ER stress and diseases Hiderou Yoshida1 2 1 Department of Biophysics Graduate Schoolof Science Kyoto University Japan 2 PRESTO-SORST Japan Science and Technology Agency Japan Keywords conformational disease cytoplasmic splicing ER stress response ER-associated protein degradation ERAD Golgi stress response Correspondence H. Yoshida Department of Biophysics Graduate School of Science Kyoto University Kitashirakawa-Oiwakecho Sakyo-ku Kyoto 606-8502 Japan Fax 81 75 753 3718 Tel 81 75 753 4201 E-mail hide@. Received 11 September 2006 revised 14 November 2006 accepted 8 December 2006 doi Proteins synthesized in the endoplasmic reticulum ER are properly folded with the assistance of ER chaperones. Malfolded proteins are disposed of by ER-associated protein degradation ERAD . When the amount of unfolded protein exceeds the folding capacity of the ER human cells activate a defense mechanism called the ER stress response which induces expression of ER chaperones and ERAD components and transiently attenuates protein synthesis to decrease the burden on the ER. It has been revealed that three independent response pathways separately regulate induction of the expression of chaperones ERAD components and translational attenuation. A malfunction of the ER stress response caused by aging genetic mutations or environmental factors can result in various diseases such as diabetes inflammation and neurodegenerative disorders including Alzheimer s disease Parkinson s disease and bipolar disorder which are collectively known as conformational diseases . In this review I will summarize recent progress in this field. Molecules that regulate the ER stress response would be potential candidates for drug targets in various conformational diseases. Abbreviations AIGP axotomy-induced glyco Golgi protein APP amyloid precursor protein ASK1 apoptosis signal-regulating kinase 1 ATF activating transcription factor .

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