The incidence of amyloid plaques, composed mainly of bamyloid peptides (Ab), does not correlate well with the severity of neurodegeneration in patients with Alzheimer's disease (AD). The effects of Ab 42 on neurons or neural stem cells (NSCs) in terms of the aggregated form remain controversial. We prepared three forms of oligomeric, fibrillar, and monomeric Ab 42 peptides and investigated their effects on the proliferation and neural differentiation of adult NSCs, according to the degree of aggregation or concentration. A low micromolar concentration (1 lmol/L) of oligomeric Ab 42 increased the proliferation of adult NSCs remarkably in a neurosphere assay. It also enhanced the neuronal differentiation of adult NSCs and their ability to migrate. These results provide us with valuable information regarding the effects of Ab 42 on NSCs in the brains of patients with AD.

Highly specific and sensitive fluorescence detection of hypochlorite in nonbiotic pure water (rapid "turn-on", ~400 fold, λ(em) ~ 560 nm) as well as in living neuronal cell cultures (neutral pH) involves oxidation of a 2-sulfide-2-benzoic acid pendent group in a new meso-thienyl-BODIPY donor-acceptor probe.

New fluorescein-based H 2 O 2 probe derivatization involves the simple dimethyl-thiocarbamoyl (DMTC) protecting group allowing for high aqueous ROS "turn-on" responses in the presence of Hg 2+ concentration.in-line spectral data, reproductions of NMR spectra, HR MS spectra. See

Novel, high "turn-on" Hg(2+) and O(2)(-) fluorescence behaviour (∼25-fold) with probes bearing [S(thi)N(py)] and [S(thi)N(py)N(py)] binding receptors, joined by oxidizable sulphides, may involve S-bound transient ROS species; such optical O(2)(-) behaviour operates moderately in neuroblastoma.

The activities of CDK5 and p35 are thought to be important in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). We studied the effect of p35 deletion in Tg2576 mice, which is an AD animal model. To obtain the desired mice, we crossed p35(-/-) with Tg2576 mice. The resulting p35(-/-)/Tg2576 (KO/Tg) mice displayed higher mortality rates and exhibited impaired spatial learning and memory at 6 months of age. Using immunohistochemical and biochemical approaches, we observed a reduction in the expression of pre- and post-synaptic markers such as NMDAR1, synaptophysin and GluR1. In addition, the intensity of MAP-2-positive dendrites extending from neuronal cell bodies was significantly decreased in KO/Tg mice compared with KO/WT and WT/Tg mice. We also detected increased neuronal cell death in the hippocampus, along with thinned and collapsed morphological changes in the alveus region and a dramatic increase in the number of microglial cells. Microglial infiltration in the hippocampus could result in the increased secretion of the soluble high mobility group box-1 protein (HMGB-1). The secretion of HMGB-1 is increased by Aβ, and secretion of HMGB-1 promotes neuronal cell death. Moreover, we found that HMGB-1 secretion induced by Aβ in KO/Tg mice gave rise to ER-mediated cell death. In summary, during the stages of KO/Tg mice model, the microglial infiltration and secretion of soluble HMGB-1 were significantly increased in the hippocampus. These conditions promote neuronal death, synaptic destruction and behavioral deficits.