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...

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...

Mutations in the presenilin-1 (PS1) gene are independent causes of familial Alzheimer's disease (AD). AD patients have dysregulated immunity, and PS1 mutant mice exhibit abnormal systemic immune responses. To test whether immune function abnormality caused by a mutant human PS1 gene (mhPS1) could modify AD-like pathology, we reconstituted immune systems of AD model mice carrying a mutant human ...

Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) are associated with early-onset familial Alzheimer's disease which displays an accelerated deposition of amyloid plaques and neurofibrillary tangles. Presenilins are multi-spanning transmembrane proteins which localize primarily to the endoplasmic reticulum and the Golgi compartments. We have previously demonstrated that PS1 exists...

BACKGROUND Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People's Republic of China. However, data regarding the effect of CEGI on Alzheimer's disease (AD) remain scarce. The present study a...

We report on the generation and phenotype of mutant alleles of multiple edematous wings (mew), the gene encoding the alpha PS1 subunit of the PS1 integrin of Drosophila. None of the six alleles examined makes detectable protein, and one allele results from a chromosome break near the middle of the translated sequence, so we are confident that we have described the null phenotype. In contrast to...

Presenilin mutations are responsible for most cases of autosomal dominant inherited forms of early onset Alzheimer disease. Presenilins play an important role in amyloid beta-precursor processing, NOTCH receptor signaling, and apoptosis. However, the molecular mechanisms by which presenilins regulate apoptosis are not fully understood. Here, we report that presenilin-1 (PS1) regulates the prote...

To assess the consequences of locus ceruleus (LC) degeneration and subsequent noradrenaline (NA) deficiency in early Alzheimer's disease (AD), mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were crossed with Ear2(-/-) mice that have a severe loss of LC neurons projecting to the hippocampus and neocortex. Testing spatial memory and hippocampal long-term potentiat...