Show simple item record

dc.contributor.authorLiu, Hui
dc.date.accessioned2012-05-18 17:44:28 (GMT)
dc.date.available2012-05-18 17:44:28 (GMT)
dc.date.issued2012-05-18T17:44:28Z
dc.date.submitted2012-05-04
dc.identifier.urihttp://hdl.handle.net/10012/6740
dc.description.abstractAβ oligomer-induced neurotoxicity has become an important area of therapeutic development in treating Alzheimer’s disease. Platelet-derived growth factor (PDGF) has been shown to be able to protect neurons against several neuronal insults such as ischemia and HIV1 toxin induced cytotoxicity. These neuroprotective effects correlate well with our previous results that demonstrate the neuroprotective effects of PDGF-BB, one of the PDGF receptor ligand subtypes, against NR2B containing NMDA receptor induced excitotoxicity, a possible underlying cause of Aβ oligomer induced synaptic dysfunction and neuronal death. This project examines the neuroprotective effect of PDGF-BB against Aβ1-42 oligomer induced cytotoxicity in both SH-SY5Y cells and primary hippocampal neurons. Cell viability was monitored by MTT assay and the affected signaling pathways were examined using pharmacological methods and Western blotting. The results demonstrated that Aβ1-42 oligomer elicited a dose-dependent toxicity with a sign of saturation at higher dosages, PDGF-BB failed to protect neurons against Aβ1-42 oligomer induced cytotoxicity. In contrast, Aβ1-42 oligomers strongly inhibit PDGF-BB induced mitogenesis in both SH-SY5Y cells and primary neurons. Further investigation using Western blotting to measure PDGF receptor expression and phosphorylation in SH-SY5Y cells showed that Aβ1-42 oligomer can inhibit PDGF-BB induced phosphorylation of PDGF β-receptor on Tyr1021, a site that is crucial for PLCγ mediated mitogenesis. These findings not only explained the poor neuroprotective effect elicited by PDGF-BB against Aβ1-42 oligomers, but also led to a novel hypothesis that Aβ1-42 oligomer may interfere with neurotrophic factor induced neuronal survival, either selectively or perhaps globally. Further exploration on this hypothesis will be able to shed light on this potentially novel mechanism of pathogenesis in Alzheimer’s disease.en
dc.language.isoenen
dc.publisherUniversity of Waterlooen
dc.subjectbeta-amyloiden
dc.subjectPlatelet-derived growth factoren
dc.subjectneurotoxicityen
dc.subjectneuroprotectionen
dc.subjectneurotrophic factoren
dc.subjectPDGF receptoren
dc.subjectAlzheimer's diseaseen
dc.titleLack of neuroprotective effects by platelet-derived growth factor against beta-amyloid induced toxicity uncovers a novel hypothesis of Alzheimer's disease pathologyen
dc.typeMaster Thesisen
dc.comment.hiddenI couldn't find my department, School of Pharmacy, and couldn't find my program, Pharmacy, either from the drop down lists.en
dc.pendingfalseen
dc.subject.programPharmacyen
uws-etd.degree.departmentSchool of Pharmacyen
uws-etd.degreeMaster of Scienceen
uws.typeOfResourceTexten
uws.peerReviewStatusUnrevieweden
uws.scholarLevelGraduateen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record


UWSpace

University of Waterloo Library
200 University Avenue West
Waterloo, Ontario, Canada N2L 3G1
519 888 4883

All items in UWSpace are protected by copyright, with all rights reserved.

DSpace software

Service outages