Henry A. Lester,Rahul Srinivasan,Christopher I. Richards,Brandon J. Henderson
申请号：
US13752228
公开号：
US20130197023A1
申请日:
2013.01.28
申请国别(地区):
US
年份:
2013
代理人:
摘要：
A method of ameliorating an endoplasmic reticulum (ER) stress response and/or unfolded protein response (UPR) in cells expressing nicotinic acetylcholine receptors (nAChRs) comprises contacting a cell expressing nAChRs with an effective amount of a ligand for nAChRs. The contacting results in attenuating endogenously expressed ATF6 translocation, expression of XBP1, phosphorylation of eukaryotic initiation factor 2α (peIF2α), increased numbers of ER exit sites, increased trafficking of known associated proteins as well as other proteins such as growth factors and their receptors, changes in abundance of selected mRNA species, and phosphorylation, abundance, or subcellular compartmentalization of other proteins involved with ER stress and/or the UPR, and inhibiting upregulation of CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) levels in the cells. The method can be used to screen for neuropharmacotherapeutic agents and to treat or prevent neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS), Parkinsons disease, Alzheimers disease, or cognitive deficiency.
