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Distribution of Nicastrin in the central nervous system of APP/PS1 double transgenic mice
Author(s) -
Luo Shifang,
He Guiqiong
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.921.7
Subject(s) - nicastrin , presenilin , amyloid precursor protein , olfactory bulb , genetically modified mouse , central nervous system , biology , transgene , neuroscience , microbiology and biotechnology , pathology , alzheimer's disease , medicine , disease , biochemistry , gene
Nicastrin (NCT) is an integral component of gamma‐secretase complex that also contains presenilin (PS), Aph‐1 and Pen‐2. gamma‐secretase is involved in the processing of over 60 substrates (eg. amyloid precursor protein, APP). Studies show that NCT is required for substrate recognition and selection of gamma‐secretase. However, little is known about its distribution in central nervous system (CNS) of APP/PS1 transgenic AD mice model and its wildtype controls. We report here, using immunoblotting and immunohistochemical methods, that NCT is widely expressed in all major areas of both AD and control mice, including olfactory bulb, cortex, hppocampus, basal ganglion, thalamus, cerebellum, brainstem and spinal cord. The NCT expression level is elevated in AD mice, and it is distributed much more extensively than circumscribed amyloid deposits. At the early stages of postnatal development, the NCT expression level is relatively high in CNS, but declined gradually in adult mice. At cellular level, NCT is localized predominantly in cell membrane and cytoplasma at early postnatal stages of AD mice, while only distributed at cell membrane in controls. Our results provide an anatomical basis to suggest that NCT may play a multifunctional role for gamma‐secretase in the developing and adult AD mice brain. This work was supported by National Natural Science Foundation of China (30700885)