Worcester Polytechnic Institute Electronic Theses and Dissertations Collection

Title page for ETD etd-071607-181533


Document Typethesis
Author Namekapoor, varun
URNetd-071607-181533
TitleMechanism of Reversal of Alzheimer’s Disease A-beta Induced Neuronal Degeneration in Cultured Human SHSY Cells Using A Neurotrophic Ependymin Mimetic.
DegreeMS
DepartmentBiology & Biotechnology
Advisors
  • David S Adams, Advisor
  • Elizabeth F Ryder, Committee Member
  • Daniel G Gibson, Committee Member
  • Keywords
  • Alzheimer's
  • Ependymins
  • Caspases
  • SOD
  • Date of Presentation/Defense2007-07-18
    Availability unrestricted

    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.

    Files
  • KapoorV.pdf

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