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Publication : Distribution and expression of Pen-2 in the central nervous system of APP/PS1 double transgenic mice.

First Author  Chu Y Year  2015
Journal  Acta Biochim Biophys Sin (Shanghai) Volume  47
Issue  4 Pages  258-66
PubMed ID  25736404 Mgi Jnum  J:318282
Mgi Id  MGI:6859053 Doi  10.1093/abbs/gmv010
Citation  Chu Y, et al. (2015) Distribution and expression of Pen-2 in the central nervous system of APP/PS1 double transgenic mice. Acta Biochim Biophys Sin (Shanghai) 47(4):258-66
abstractText  The gamma-secretase complex catalyzes the final cleavage step of amyloid beta-protein precursor (APP) to generate amyloid beta (Abeta) peptide, a pathogenic component of senile plaques in the brain of Alzheimer's disease (AD) patients. Recent studies have shown that presenilin enhancer-2 (Pen-2), presenilin (PS, including PS1 and PS2), nicastrin, and anterior pharynx-defective 1 are essential components of the gamma-secretase. The structure and function of Pen-2 in vitro have been well defined. However, little is known about the neuroanatomical distribution and expression of Pen-2 in the central nervous system (CNS) of AD model mice. We report here, using various methods such as immunohistochemical staining and immunoblotting, that Pen-2 is widely expressed at specific neuronal cells of major areas in AD model mice, including the olfactory bulb, basal forebrain, striatum, cortex, hippocampus, amygdala, thalamus, hypothalamus, cerebellum, brainstem, and spinal cord. It is co-expressed with PS1 in specific neuronal cells in mouse brain. Pen-2 is distributed much more extensively than extracellular amyloid deposits, suggesting the importance of other factors in localized amyloid deposition. Pen-2 is localized predominantly in cell membrane and cytoplasma in adult AD mice, but only distributed at cell membrane in controls. At the early stages of postnatal development, the expression level of Pen-2 is relatively high in CNS, but declines, gradually in adult mice. The present study provides an anatomical basis for Pen-2 as a key component of gamma-secretase complex in the brain of developing and adult mice, and Pen-2 might be closely related to Abeta burden in aging nervous system.
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