Program Project on Cellular Cofactors, Neuronal Stress & Rescue, Aging & Alzheimer Disease

The Program Project on Cellular Cofactors, Neuronal Stress & Rescue, Aging & Alzheimer Disease was transferred from Columbia University, New York in 2011 when Dr. Shi Du Yan became a faculty member at the University of Kansas.  The program, supported by a grant from the National Institute on Aging of the National Institutes of Health, ended in June 2015.

Goal

Cell associated cofactors, RAGE (Receptor for AGEs) and ABAD (AB binding alcohol dehydrogenase) are critical for concentrating the effects of low levels of Afi, relevant to early stages of pathogenicity in Alzheimer's disease (AD) on vulnerable cells.   During the first phase, experimental evidence to support a link between RAGE or ABAD and AlJ-mediated cell stress were provided.  The goal of the second Phase of the Program Project was to further elucidate the mechanisms of RAGE /ABAD-mediated cell stress & rescue relevant to Aging and the Nervous System.

Cores

Administrative, Biostatistics & Data Management Core 

Core A was responsible for the administration of the program project and for providing data management services and statistical analysis. 

The core leader was Dr. Shi Du Yan, professor of pharmacology and toxicology at KU.

Transgenic Mouse, protein analysis, behavior and neuropathology 

Core B assisted in maintaining and producing transgenic animals for the proposed studies. The Core Maintained breeding stocks (projects 1-2-3), performing backcrossing (project 3) and crossbreeding (project 1-2-3) to produce strains needed for the proposed studies.  

The core leader was Dr. Shi Du Yan, professor of pharmacology and toxicology at KU.

Behavioral and Neuropathologic Core  

Core C undertook the behavioral analysis of transgenic mice for the projects 1 & 3 and to undertook neuropathologic analysis of murine brain samples from transgenic animals.  

The core leader was Dr. Shi Du Yan, professor of pharmacology and toxicology at KU.

Projects

RAGE and Aβ-induced cell stress: Transgenic Models  

The specific aims of the project was to investigate the role of RAGE in Aβ-mediated neuronal and synaptic dysfunction in transgenic Alzheimer mouse model. 

The project leader was Dr. Shi Du Yan, professor of pharmacology and toxicology at KU.

Project 2: RAGE, nerve injury, regeneration, diabetics, and aging 

Project 2 examined the impact of RAGE in neuronal repair mechanisms in the peripheral nervous system affected by chronic accumulation of RAGE ligands, Advanced Glycation Endproducts, in diabetes. 

The project leader was Dr. Ann Marie Schmidt, professor of medicine and pharmacology at New York University School of Medicine.

ABAD and Aß-induced cell stress and synaptic dysfunction

The goal of this project was to investigate the mechansim underlying ABAD/Aβ-mediated synaptic dysfunction and to determine whether inhibition of ABAD-Aβ interaction protects against cognitive and synaptic impariments due to Aβ elevation. 

The project leader was Dr. Ottavio Arancio, associate professor of pathology at Columbia University in New York.

Structural and Functional Properties

The goal of Project 4 was to probe the surface interface of ABAD-Aβ and ABAD-cyclophilin D (CypD) using structural analyses and to analyze critical aspects of the intracellular pathway through which ABAD engages Aβ, CypD and the metabolite 1-methyl-4-phenylpyridinium (MPP) and the ABAD-Aβ complex all induce cellular stress. 

The project leader was Dr. Joyce Lustbader, adjunct professor of the obstetric and gynecology at the Columbia University College of Physicians, New York.