Distinct amyloid precursor protein processing machineries of the olfactory system

Biochemical and Biophysical Research Communications
Jae Yeon KimCheil Moon

Abstract

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...Continue Reading

Citations

Jun 16, 2018·Current Allergy and Asthma Reports·Concepció MarinJoaquim Mullol
Feb 6, 2020·Journal of Toxicology and Environmental Health. Part a·Rui ZhangHe Wang
Aug 10, 2019·Frontiers in Neuroscience·Ximena CastilloMarietta Zille
Jul 11, 2018·Dementia & Neuropsychologia·Maren de Moraes E SilvaRenata Ramina Pessoa
Nov 21, 2019·Journal of Alzheimer's Disease : JAD·Mahraz Parvand, Catharine H Rankin
Jun 9, 2020·Frontiers in Neuroscience·Michele DibattistaJohannes Reisert

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