Mini-chromosome maintenance (MCM) proteins form complexes that are required for DNA replication and are highly conserved throughout evolution. The replicative helicase of eukaryotic organisms is composed of the six paralogs MCM2-7, which form a heterohexameric ring structure. In contrast, the structure of the archaean replicative MCM helicase is a single Mcm protein that forms a homohexameric c...

Missense mutations in two related genes, termed presenilin 1 (PS1) and presenilin 2 (PS2), cause dementia in a subset of early-onset familial Alzheimer's disease (FAD) pedigrees. In a variety of experimental in vitro and in vivo settings, FAD-linked presenilin variants influence the processing of the amyloid precursor protein (APP), leading to elevated levels of the highly fibrillogenic Abeta1-...

Background Late onset degenerative dementia is a growing, common and complex disorder in which the aetiological role played by environment and genes has not yet been established. A familial component is frequently ascertained in Alzheimer’s disease (AD) (30% of first degree relatives affected) and also in Frontotemporal Dementia (FTD) (40-60%). Early onset degenerative dementia has sometimes be...

Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms un...

Current evidence indicates that excess brain cholesterol regulates amyloid-β (Aβ) deposition, which in turn can regulate cholesterol homeostasis. Moreover, Aβ neurotoxicity is potentiated, in part, by mitochondrial glutathione (mGSH) depletion. To better understand the relationship between alterations in cholesterol homeostasis and Alzheimer's disease (AD), we generated a triple transgenic mice...

BACKGROUND/AIMS Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understoo...

P (PS) 1 and 2 play a key role in the pathogenesis of Alzheimer’s disease (AD) by being essential for the intramembrane cleavage of amyloid precusor protein (APP), thus releasing the pathogenic Ab peptides into the intercellular space (1). Recently, PS1 has been shown to exert an unusual aspartyl protease activity, possibly forming the active center of the g secretase, one of the prime drug tar...

The Amer Belt, hosting eleven informal formations of the supergroup, is proposed as type area for four regional Paleoproterozoic sequences (Ps1–Ps4) in central Rae Craton, western Churchill Province. ca. 1.9–1.865 Ga Snowbird orogeny (D P1 ) affected only Ps1–Ps3, whereas 1.87–1.81 Hudsonian P2 all four. Sequence Ps1 Ayagaq Lake formation (<2.3 quartzite) initiates schistose basal polymict o...

Children represent one of the most vulnerable groups in society. The detailed characterization of pollution (both indoors and outdoors) of schools is of great importance, since it may allow preventing potential risks to children health. Yet the information related to carcinogenic compounds, such as some polycyclic aromatic hydrocarbons (PAHs) in child educational settings is very limited. Thus ...

Glycogen synthase kinase 3 (GSK-3) dysregulation is implicated in the two Alzheimer's disease (AD) pathological hallmarks: beta-amyloid plaques and neurofibrillary tangles. GSK-3 inhibitors may abrogate AD pathology by inhibiting amyloidogenic gamma-secretase cleavage of amyloid precursor protein (APP). Here, we report that the citrus bioflavonoid luteolin reduces amyloid-beta (Abeta) peptide g...