Article history: Received on: 28/01/2014 Revised on: 17/02/2014 Accepted on: 09/03/2014 Available online: 28/07/2014 Polysaccharides from mushroom Pleurotus sajor-caju (PS1) and Lactuca Sativa (PS2) were isolated and purified (22.40 and 26.80g/100g respectively). Cytotoxic activities of PS1 and PS2 were examined In vitro using colon (HCT 116), liver (HEPG2), cervical (HELA) and breast (MCF7) ca...

Presenilin 1 (PS1), a causative molecule of familial Alzheimer's disease (AD), is known to be an unprimed substrate of GSK3 (Twomey et al. 2006) and is phosphorylated at serine 353, 357 residues in its cytoplasmic loop region (Kirschenbaum et al. 2001). In this report, we investigated the effect of PS1 phosphorylation on AD pathophysiology and obtained two important results – PS1 phosphorylati...

Although an excitotoxic mechanism of neuronal injury has been proposed to play a role in chronic neurodegenerative disorders such as Alzheimer's disease, and neurotrophic factors have been put forward as potential therapeutic agents, direct evidence is lacking. Taking advantage of the fact that mutations in the presenilin-1 (PS1) gene are causally linked to many cases of early-onset inherited A...

ABCA1-deficient mice have low levels of poorly lipidated apolipoprotein E (apoE) and exhibit increased amyloid load. To test whether excess ABCA1 protects from amyloid deposition, we crossed APP/PS1 mice to ABCA1 bacterial artificial chromosome (BAC) transgenic mice. Compared with wild-type animals, the ABCA1 BAC led to a 50% increase in cortical ABCA1 protein and a 15% increase in apoE abundan...

Mutant presenilin-1 (PS1) increases amyloid peptide production, attenuates capacitative calcium entry (CCE), and augments calcium release from the endoplasmatic reticulum (ER). Here we measured the intracellular free Ca(2+) concentration in hippocampal neurons from six different combinations of transgenic and gene-ablated mice to demonstrate that mutant PS1 attenuated CCE directly, independent ...

BACKGROUND Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD). MATERIALS AND METHODS We characterized the cellular localization and endoproteolysis of presenilin 2 (PS2) and presenilin 1 (PS1) in brains from 25 individuals with presenilin-mutations causing FAD, as well as neurologically normal individuals and individuals with sporadic Alzheimer's diseas...

Pathogenic mutations in presenilin 1 (PS1) are associated with approximately 50% of early-onset familial Alzheimer disease. PS1 is endoproteolytically cleaved to yield a 30-kDa N-terminal fragment (NTF) and an 18-kDa C-terminal fragment (CTF). Using COS7 cells transfected with human PS1, we have found that phorbol 12, 13-dibutyrate and forskolin increase the state of phosphorylation of serine r...

We have developed a presenilin-1 (PS1) conditional knockout mouse (cKO), in which PS1 inactivation is restricted to the postnatal forebrain. The PS1 cKO mouse is viable and exhibits no gross abnormalities. The carboxy-terminal fragments of the amyloid precursor protein differentially accumulate in the cerebral cortex of cKO mice, while generation of beta-amyloid peptides is reduced. Expression ...

The Notch family of proteins consists of transmembrane receptors that play a critical role in the determination of cell fate. Genetic studies in Caenorhabditis elegans suggest that the presenilin proteins, which are associated with familial Alzheimer's disease, regulate Notch signaling. Here we show that proteolytic release of the Notch-1 intracellular domain (NICD), an essential step in the ac...

Presenilin-1 (PS1) and presenilin-2 (PS2), the major genes of familial Alzheimer's disease, are homologous to sel-12, a Caenorhabditis elegans gene involved in cell fate decision during development. Recently, wild-type and mutant presenilins have been associated also with apoptotic cell death. By using stable transfection of antisense cDNAs, we studied the functions of PS1 and PS2 during neuron...