Distribution and expression of Pen-2 in the central nervous system of APP/PS1 double transgenic mice.
The γ-secretase complex catalyzes the final cleavage step of amyloid β-protein precursor (APP) to generate amyloid β (Aβ) 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 γ-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 γ-secretase complex in the brain of developing and adult mice, and Pen-2 might be closely related to Aβ burden in aging nervous system.
Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
Yanan
Y
Chu
Department of Radiology, Pediatric Hospital, Chongqing Medical University, Chongqing 400016, China.
Xuehua
X
Peng
Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
Zhiming
Z
Long
Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
Kejian
K
Wang
Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
Shifang
S
Luo
Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
Akhilesh
A
Sharma
Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China Department of Anatomy, Chongqing Medical University, Chongqing 400016, China guiqionghe@hotmail.com.
Guiqiong
G
He
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002490:Central Nervous System / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009154:Mutation; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
C545487:APP protein, human; D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; C555827:presenilin enhancer 2, mouse
Alzheimer's disease; central nervous system; distribution; presenilin enhancer-2; γ-secretase