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Neuromodulation by a N-Terminal Beta Amyloid Fragment
|Title:||Neuromodulation by a N-Terminal Beta Amyloid Fragment|
|Contributors:||Nichols, Robert (advisor)|
|Keywords:||beta amyloid (Aβ)|
N-terminal Aβ fragment (Aβ1-15)
|Date Issued:||26 Sep 2014|
|Publisher:||University of Hawaii at Manoa|
|Abstract:||Beta amyloid (Aβ), a polypeptide found in the brain consisting of 38-43 amino acids, is generated via proteolytic cleavage of amyloid precursor protein (APP). Although multiple isoforms of Aβ exist, the 1-42 amino acid isoform (Aβ1-42) has been found to be the primary neurotoxic species in Alzheimer’s disease, formed via cleavage of APP by β-secretase and γ-secretase. However, it has been shown that a non-amyloidogenic pathway exists wherein Aβ is cleaved by another protease, α-secretase, ultimately resulting in the generation of a 1-15 amino acid fragment, termed the N-terminal Aβ fragment (Aβ1-15). It has shown that inhibition of γ-secretase leads to upregulation of α-secretase activity, possibly leading to increased levels of the N-terminal Aβ fragment. More intriguingly, the Aβ1-15 fragment may function as a potent non-toxic, neuromodulator. Thus, I am investigating: (1) the pathways involved in the regulation of production of the N-terminal beta amyloid fragment with a particular focus on the alpha secretase pathway and its potential modulation by regulators of alpha secretase activity and (2) whether the upregulation of the N-terminal beta amyloid fragment in culture is neuroprotective and/or neuromodulatory. Using immunoblot analysis, we have shown production of APP in FLAG-tagged APP-transfected neuroblastoma cells. In addition, preliminary results suggest that treatment with the γ-secretase inhibitor DAPT leads to greater processing of APP and possible generation of Aβ1-15. We anticipate the Aβ1-15 activity to lead to neuromodulation of nerve cell function.|
|Pages/Duration:||iv, 35 pages|
|Rights:||All UHM Honors Projects are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.|
|Appears in Collections:||
Honors Projects for Biology|
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