Abstract

One objective of these studies is to understand the structure of the acetylcholine receptor molecule and the mechanism by which it functions. Monoclonal antibodies are being used as probes of receptor structure and function. The function of receptor reconstituted into model membranes is being studied. The other major objective of these studies is to understand and control the pathological mechanisms by which an autoimmune response to receptor develops and impairs neuromuscular transmission in myasthenia gravis (MG). Experimental autoimmune myasthenia gravis (EAMG) is an excellent animal model of MG which we have used to learn much about MG. Techniques derived from immunochemical studies of the receptor molecule are being applied to provide an understanding of the molecular biology of MG and EAMG.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS011323-18
Application #
3394456
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1976-09-01
Project End
1991-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
18
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Wang, Jingyi; Kuryatov, Alexander; Lindstrom, Jon (2015) Expression of cloned ?6* nicotinic acetylcholine receptors. Neuropharmacology 96:194-204
Afshordel, Sarah; Wood, Wellington Gibson; Igbavboa, Urule et al. (2014) Impaired geranylgeranyltransferase-I regulation reduces membrane-associated Rho protein levels in aged mouse brain. J Neurochem 129:732-42
Hussmann, G Patrick; DeDominicis, Kristen E; Turner, Jill R et al. (2014) Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain. J Neurochem 129:721-31
Eaton, J Brek; Lucero, Linda M; Stratton, Harrison et al. (2014) The unique ?4+/-?4 agonist binding site in (?4)3(?2)2 subtype nicotinic acetylcholine receptors permits differential agonist desensitization pharmacology versus the (?4)2(?2)3 subtype. J Pharmacol Exp Ther 348:46-58
Ley, Carson Kai-Kwong; Kuryatov, Alexander; Wang, Jingyi et al. (2014) Efficient expression of functional (?6?2)2?3 AChRs in Xenopus oocytes from free subunits using slightly modified ?6 subunits. PLoS One 9:e103244
Kuryatov, Alexander; Mukherjee, Jayanta; Lindstrom, Jon (2013) Chemical chaperones exceed the chaperone effects of RIC-3 in promoting assembly of functional ?7 AChRs. PLoS One 8:e62246
O'Neill, Heidi C; Laverty, Duncan C; Patzlaff, Natalie E et al. (2013) Mice expressing the ADNFLE valine 287 leucine mutation of the ?2 nicotinic acetylcholine receptor subunit display increased sensitivity to acute nicotine administration and altered presynaptic nicotinic receptor function. Pharmacol Biochem Behav 103:603-21
McClure-Begley, Tristan D; Stone, Kathy L; Marks, Michael J et al. (2013) Exploring the nicotinic acetylcholine receptor-associated proteome with iTRAQ and transgenic mice. Genomics Proteomics Bioinformatics 11:207-18
Luo, Jie; Lindstrom, Jon (2012) Myasthenogenicity of the main immunogenic region and endogenous muscle nicotinic acetylcholine receptors. Autoimmunity 45:245-52
Lindstrom, Jon; Luo, Jie (2012) Myasthenogenicity of the main immunogenic region. Ann N Y Acad Sci 1274:9-13

Showing the most recent 10 out of 158 publications