Faculty Advisor or Committee Member

David S. Adams, Advisor

Faculty Advisor or Committee Member

Elizabeth F. Ryder, Committee Member

Faculty Advisor or Committee Member

Daniel G. Gibson III, Committee Member

Identifier

etd-071607-181533

Abstract

"Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to dementia in adults. The mechanism of neurodegeneration is thought to involve the extracellular production of a highly toxic A-beta peptide that engages cell surface receptors to induce cellular oxidative stress and apoptosis, but the signal transduction pathways that lead to A-beta induced cell death are unknown. We previously showed that a human ependymin neurotrophic peptide mimetic (hEPN-1) can promote cell survival in an in vitro AD model system. This initial observation was extended in this thesis by investigating the mechanism of A-beta induced apoptosis and hEPN-1 induced survival. Immunoblots were used to assay the total cellular levels of specific caspase proteins. The results show that A-beta induced apoptosis uses an extrinsic caspase pathway involving caspases-2 and -3, and that hEPN-1 treatment can reduce those caspase levels. A caspase activity assay showed that A-beta increased caspase-3/7 activity, while hEPN-1 treatment lowered it. Moreover, in vivo studies with AD transgenic mice showed that hEPN-1 treatment increased antioxidative superoxide dismutase levels in brain. Thus, hEPN-1 holds potential as a therapeutic to treat the underlying neurodegenerative cause of AD, not merely its symptoms as with other currently approved AD drugs."

Publisher

Worcester Polytechnic Institute

Degree Name

MS

Department

Biology & Biotechnology

Project Type

Thesis

Date Accepted

2007-07-16

Accessibility

Unrestricted

Subjects

Alzheimer's, Ependymins, Caspases, SOD, Alzheimer's disease, Molecular aspects, Apoptosis, Ependymin, Caspases

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