Amyloid beta-peptide (Abeta) is generated by the consecutive cleavages of beta- and gamma-secretase. The intramembraneous gamma-secretase cleavage critically depends on the activity of presenilins (PS1 and PS2). Although there is evidence that PSs are aspartyl proteases with gamma-secretase activity, it remains controversial whether their subcellular localization overlaps with the cellular site...

Besides cognitive decline and behavioral alteration, urinary incontinence often occurs in patients suffering from Alzheimer's disease (AD). To determine whether the transgenic mouse model of AD, APP/PS1 (APP(SL)/PS1(M146L)) mouse, shows alteration of the urinary bladder function and anxiety, as for patients with AD, we examined the urinary marking behavior in relation to affective behavior. At ...

We report a PS1 gene mutation (Val 97Leu) in a Chinese familial Alzheimer's disease (FAD) pedigree and a cell model of FAD built by transfecting PS1 v97L mutants into human neuroblastoma SH-SY5Y cells. To test our hypothesis that the PS1 v97L mutation is pathogenic, we investigated possible alterations in transport regulation and intracellular Ca(2+) homeostasis in endoplasmic reticulum (ER). G...

Alzheimer's disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which is generated through sequential proteolysis of the amyloid precursor protein (APP), first by the action of β-secretase, generating the β-C-terminal fragment (βCTF), and then by the Presenilin 1 (PS1) enzyme in the γ-secretase complex, generating Aβ. γ-Secretase is an intramembranous protein complex co...

Jie Shen: We hope that if we can understand how PS1 regulates the cell cycle of neural progenitor cells during development, we might be able to figure out how PS1 regulates the cell cycle and fate of neural stem cells in the adult, which may be relevant to AD pathogenesis. Although PS1 is required for the regulation of the cell cycle, overexpression of PS1 may not have gain-offunction effects. ...

Presenilin 1 (PS1) is an essential γ-secretase component, the enzyme responsible for amyloid precursor protein (APP) intramembraneous cleavage. Mutations in PS1 lead to dominant-inheritance of early-onset familial Alzheimer's disease (FAD). Although expression of FAD-linked PS1 mutations enhances toxic Aβ production, the importance of other APP metabolites and γ-secretase substrates in the etio...

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...