Conditional forebrain inactivation of nicastrin causes progressive memory impairment and age-related neurodegeneration.
AuthorsTabuchi K, Chen G, Südhof TC, Shen J,
JournalJ Neurosci
PubMed ID19494151
'Loss of presenilin function in adult mouse brains causes memory loss and age-related neurodegeneration. Since presenilin possesses gamma-secretase-dependent and -independent activities, it remains unknown which activity is required for presenilin-dependent memory formation and neuronal survival. To address this question, we generated postnatal forebrain-specific nicastrin conditional knock-out (cKO) mice, in which ... More
EphB signaling regulates target innervation in the developing and deafferented auditory brainstem.
AuthorsNakamura PA, Hsieh CY, Cramer KS,
JournalDev Neurobiol
PubMed ID22021100
'Precision in auditory brainstem connectivity underlies sound localization. Cochlear activity is transmitted to the ventral cochlear nucleus (VCN) in the mammalian brainstem via the auditory nerve. VCN globular bushy cells project to the contralateral medial nucleus of the trapezoid body (MNTB), where specialized axons terminals, the calyces of Held, encapsulate ... More
Transcriptional regulation of PEN-2, a key component of the gamma-secretase complex, by CREB.
AuthorsWang R, Zhang YW, Sun P, Liu R, Zhang X, Zhang X, Xia K, Xia J, Xu H, Zhang Z,
JournalMol Cell Biol
PubMed ID16449647
'Gamma-secretase, which is responsible for the intramembranous cleavage of Alzheimer''s beta-amyloid precursor protein (APP), the signaling receptor Notch, and many other substrates, is a multiprotein complex consisting of at least four components: presenilin (PS), nicastrin, APH-1, and PEN-2. Despite the fact that PEN-2 is known to mediate endoproteolytic cleavage of ... More
Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components.
AuthorsZhang YW, Luo WJ, Wang H, Lin P, Vetrivel KS, Liao F, Li F, Wong PC, Farquhar MG, Thinakaran G, Xu H,
JournalJ Biol Chem
PubMed ID15711015
'gamma-Secretase, which is responsible for the intramembranous cleavage of Alzheimer beta-amyloid precursor protein and the signaling receptor Notch, is a multiprotein complex consisting of at least four components: presenilin (PS); nicastrin (Nct); APH-1 (anterior pharynx-defective-1); and presenilin enhancer-2 (PEN-2). Presenilin 1 (PS1) is known to be essential for the stability, ... More