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METHOD FOR SCREENING SUBSTANCE RELATING TO ENDOPLASMIC RETICULUM STRESS PARTICIPATING IN ONSET OF DIABETES

外国特許コード F130007206
整理番号 S2011-0221-C0
掲載日 2013年3月7日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2012JP052650
国際公開番号 WO 2012108394
国際出願日 平成24年2月6日(2012.2.6)
国際公開日 平成24年8月16日(2012.8.16)
優先権データ
  • 特願2011-023697 (2011.2.7) JP
発明の名称 (英語) METHOD FOR SCREENING SUBSTANCE RELATING TO ENDOPLASMIC RETICULUM STRESS PARTICIPATING IN ONSET OF DIABETES
発明の概要(英語) The purpose of the present invention is to provide a system for evaluating the activation of an ATF6-mediated pathway. Namely, provided is a method for screening an endoplasmic reticulum stressor that is capable of activating the ATF6-mediated pathway. Also provided are a method for screening a substance that is capable of regulating endoplasmic reticulum stress induced by the activation of the ATF6-mediated pathway, and a method for screening an antidiabetic drug candidate. As the results of intensive studies, the present inventors found that the activation of the ATF6-mediated pathway can be evaluated in the state of vital cells in real time at a high sensitivity by using a polynucleotide that encodes a non-fluorescent peptide domain derived from a fluorescent protein and an ATF6 protein domain.
従来技術、競合技術の概要(英語) BACKGROUND ART
As the biological stress the diabetic related to oxidative stress are known and, in recent years, it has been found that the endoplasmic reticulum as another stress, in the same manner as with oxidative stress, involvement in diabetes has been increasingly recognized.
Is the endoplasmic reticulum, being synthesized within the endoplasmic reticulum unstable protein raw in physical, chemical stimulation by failure in the construction of the normal folded structure, aberrant protein to the endoplasmic reticulum and accumulates to a state. In the endoplasmic reticulum, physical instability of the protein during biosynthesis, susceptible to chemical stimulation, an abnormal stimulation changes to aberrant protein folding structure. Protein is properly folded in the endoplasmic reticulum to the Golgi is which is transported, the aberrant protein folding is failed to be stored in the endoplasmic reticulum.
Cells, to the endoplasmic reticulum such, usually at least the following two variants of a method 3 is thought to be against. (1) Increased by increasing the molecular chaperones in the endoplasmic reticulum, to protect the protein accumulated in the endoplasmic reticulum (UPR: unfolded protein response) into the reduced protein to the endoplasmic reticulum ; (2), reducing the load on the accumulated protein in the endoplasmic reticulum ; (3) cytoplasmic degradation (ERAD: ER associated protein degradation).
However, to these defense mechanisms mechanisms that, in the case where the stress is much larger, or be a question somewhere in the defense mechanism does not work as well, a certain type of cell death are believed to occur. Derived from such cell death is characterized in that the endoplasmic reticulum, morphological features of apoptosis, also CHOP, JNK, the induction of expression of a molecule called caspase, or it can be associated with activation.
In recent years, cell death is derived from the endoplasmic reticulum, diabetes, Parkinson's disease and Alzheimer's disease, polyglutamine disease, prion disease, amyotrophic lateral sclerosis (ALS) raw device such as a neurodegenerative disease, ischemic disease such as deeply involved with various pathological states has been revealed. Therefore, the endoplasmic reticulum-derived cell death to overcome, to a variety of diseases, to provide a new therapies considered.
Therefore, the conditions as described above from, for example the endoplasmic reticulum or endoplasmic reticulum stress measurement method which affect the search in various studies has been made (for example, refer to Patent Document 4 Patent Document 1 -) is, regarding the mechanism of the endoplasmic reticulum even if the current, which are involved in how the matter to be, is far from less known.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • TOKUSHIMA UNIVERSITY
  • 発明者(英語)
  • OYADOMARI, Seiichi
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
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