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Dementia 2016
September 29-October 01, 2016
Volume 6 Issue 5(Suppl) J Alzheimers Dis Parkinsonism 2016
ISSN:2161-0460 JADP, an open access journal
conferenceseries .com
September 29-October 01, 2016 London, UK
5th International Conference on
Alzheimer’s Disease & Dementia
Harkkyun Kim, J Alzheimers Dis Parkinsonism 2016, 6:5(Suppl)
Oxidative modification of γ-secretase enhances amyloidogenic pathway
Harkkyun Kim
Sungkyunkwan University School of Pharmacy, Republic of Korea
The cause of elevated level of amyloid beta-peptide (Aβ42) in common late-onset sporadic Alzheimer’s disease (AD] has
not been established. Here, we show that the membrane lipid peroxidation product 4-hydroxynonenal (HNE) is associated
with amyloid and neurodegenerative pathologies in AD and that it enhances gamma-secretase activity and Aβ42 production
in neurons. The gamma-secretase substrate receptor, nicastrin, was found to be modified by HNE in cultured neurons and in
brain specimens from patients with AD, in which HNE–nicastrin levels were found to be correlated with increased gamma-
secretase activity and Abeta plaque burden. Furthermore, HNE modification of nicastrin enhanced its binding to the gamma-
secretase substrate, amyloid precursor protein (APP) C99. In addition, the stimulation of gamma-secretase activity and Aβ42
production by HNE were blocked by an HNE-scavenging histidine analog in a 3xTg-AD mouse model of AD. These findings
suggest a specific molecular mechanism by which oxidative stress increases Aβ42 production in AD and identify HNE as a
novel therapeutic target upstream of the gamma-secretase cleavage of APP.
Biography
Harkkyun Kim has completed his BS degree at the age of 26 years and is studying Molecular Cellular Biology from Sungkyunkwan University School of Pharmacy.
Now he is Ph.D candidiate studying molecular pathogenesis of Alzheimer’s disease, especially about the relationship between adiponectin and Alzheimer’s
disease.