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Distinct amyloid precursor protein processing machineries of the olfactory system

Distinct amyloid precursor protein processing machineries of the olfactory system
Kim, Jae YeonRasheed, Ameer Abu BakrYoo, Seung JunKim, So YeonCho, BongkiSon, Go WoonYu, Seong WoonChang, Keun-ASuh, Yoo-HunMoon, Cheil
DGIST Authors
Kim, Jae Yeon; Rasheed, Ameer Abu Bakr; Yoo, Seung Jun; Kim, So Yeon; Cho, Bongki; Son, Go Woon; Yu, Seong Woon; Chang, Keun-A; Suh, Yoo-Hun; Moon, Cheil
Issue Date
Biochemical and Biophysical Research Communications, 495(1), 533-538
Article Type
Author Keywords
Alzheimer&aposs disease(AD)Amyloid precursor protein(APP)Olfactory systemOlfactory epithelium(OE)gamma-SecretasePresenilin
Processing of amyloid precursor protein (APP) occurs through sequential cleavages first by β-secretase and then by the γ-secretase complex. However, abnormal processing of APP leads to excessive production of β-amyloid (Aβ) in the central nervous system (CNS), an event which is regarded as a primary cause of Alzheimer's disease (AD). In particular, gene mutations of the γ-secretase complex—which contains presenilin 1 or 2 as the catalytic core—could trigger marked Aβ accumulation. Olfactory dysfunction usually occurs before the onset of typical AD-related symptoms (eg, memory loss or muscle retardation), suggesting that the olfactory system may be one of the most vulnerable regions to AD. To date however, little is known about why the olfactory system is affected so early by AD prior to other regions. Thus, we examined the distribution of secretases and levels of APP processing in the olfactory system under either healthy or pathological conditions. Here, we show that the olfactory system has distinct APP processing machineries. In particular, we identified higher expressions levels and activity of γ-secretase in the olfactory epithelium (OE) than other regions of the brain. Moreover, APP c-terminal fragments (CTF) are markedly detected. During AD progression, we note increased expression of presenilin2 of γ-secretases in the OE, not in the OB, and show that neurotoxic Aβ*56 accumulates more quickly in the OE. Taken together, these results suggest that the olfactory system has distinct APP processing machineries under healthy and pathological conditions. This finding may provide a crucial understanding of the unique APP-processing mechanisms in the olfactory system, and further highlights the correlation between olfactory deficits and AD symptoms. © 2017 Elsevier Inc.
Academic Press
Related Researcher
  • Author Yu, Seong-Woon Laboratory of Neuronal Cell Death
  • Research Interests Molecular mechanisms of neuronal cell death and neurodegeneration
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Division of Biotechnology1. Journal Articles
Department of Brain SciencesLaboratory of Neuronal Cell Death1. Journal Articles
Department of Brain SciencesLaboratory of Chemical Senses1. Journal Articles

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