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

Abstract

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.

Methylation differences in Alzheimer’s disease neuropathologic change in the aged human brain

“…Nevertheless, our small IHC experiment showed that in a brain with ADNC, PEN-2 was highly expressed in the hippocampus and substantia nigra. In contrast to findings in mouse models of AD, we did not see expression in cerebellum and pons [ 68 ].…”

Effects and Mechanism of Huannao Yicong Decoction Extract on the Ethology of Transgenic APP/PS1 Mice

“…PEN-2 is widely expressed in specific nerve cells of most brain areas of transgenic APP/PS1 mice, including the olfactory bulb, basal ganglia, striatum, cortex, hippocampus, amygdala, thalamus, hypothalamus, cerebellum, brainstem, and spinal cord. It is not only the main component of γ -secretase, but also the modulator of γ -secretase activity, playing a key role in the production of A β 1-42 [ 21 – 23 ]. CREB, a transcription regulatory factor of PEN-2, which can activate some specific genes to produce proteins, strengthens the connection between cells and is closely related to the formation and maintaining of long-term memory [ 24 ].…”