Aluminum (Al) compounds are neurotoxic and have been shown to induce experimental neurodegeneration although the mechanism of this effect is unclear. In order to study this neurotoxic effect of Al, we have developed an in vitro model system using Al maltolate and human NT2 cells. Al maltolate at 500 microM caused significant cell death with a 24-h incubation and this toxicity was even more evid...

The study reported in the present issue of the Journal of Alzheimer’s disease by Mizoroki et al. [8] concludes that the failure of treatment of transgenic mice with aluminum maltolate to induce Alzheimer’s-like neuropathological changes provides proof that aluminum is not a causative agent in the etiology of Alzheimer’s disease. In our opinion, this report by Mizoroki et al. fails to provide an...

Neurodegenerative diseases, including Alzheimer's disease, are characterized by a progressive and selective loss of neurons. Apoptosis under mitochondrial control has been implicated in this neuronal death process, involving the release of cytochrome c into the cytoplasm and initiation of the apoptosis cascade. However, a growing body of evidence suggests an active role for the endoplasmic reti...

Synapse loss and neuronal death are key features of Alzheimer's disease pathology. Disrupted axonal transport of mitochondria is a potential mechanism that could contribute to both. As the major producer of ATP in the cell, transport of mitochondria to the synapse is required for synapse maintenance. However, mitochondria also play an important role in the regulation of apoptosis. Investigation...

OBJECTIVE To explore the role of RAS/PI3K pathway in the impairment of long-term potentiation (LTP) induced by acute aluminum (Al) treatment in rats in vivo. METHODS First, different dosages of aluminum-maltolate complex [Al(mal)3] were given to rats via acute intracerebroventricular (i.c.v.) injection. Following Al exposure, the RAS activity of rat hippocampus were detected by ELISA assay af...

Aluminum (Al) can cause neurotoxicity, a low-turnover osteomalacia, and microcytic anemia. To test the null hypothesis that the chemical form (species) of Al does not influence its mechanism or rate of absorption from the gastrointestinal tract, Al flux across and uptake into Caco-2 cells was investigated. Caco-2 cells were grown on porous membranes mounted in vertical diffusion chambers or in ...

Intracisternal administration of aluminum maltolate induces biochemical and histological changes in the rabbit brain. The primary histological response to this aluminum intoxication is the appearance within many neuronal somata and dendrites of intensely argyrophilic masses of fibrillar material. Ultrastructural examination of these bodies in both conventionally-prepared and silver-stained sect...

Clinical studies have shown gallium nitrate to have significant antitumor activity against non-Hodgkin's lymphoma and bladder cancer, thus indicating that gallium-based drugs have potential for further development as antineoplastic agents. In this study, we compared the cytotoxicity of gallium maltolate, a novel gallium compound, with gallium nitrate in lymphoma cell lines, including p53 varian...

To observe the characteristic changes of PGE2-EPs pathway and divergent functions of PGE2 receptor subtypes on neuronal injury. The primary cultured rat hippocampus neuron injury model was established via aluminum maltolate (100 μM). The aluminum-overload neurons were treated with the agonists of EP1 (17-phenyl trinor Prostaglandin E2 ethyl amide), EP2 (Butaprost), EP3 (Sulprostone) and EP4 (CA...