Mechanism underlying anti-hyperalgesic and anti-allodynic properties of anomalin in both acute and chronic inflammatory pain models in mice through inhibition of NF-κB, MAPKs and CREB signaling cascades.

The focus of this chapter will be directed at similarities between aluminium and iron, both from a chemical and biochemical view point, and a discussion of whether the accumulation of aluminium in the brain of Alzheimer patients is due to its capacity to use specific iron protein carrier systems. Brain iron is elevated in many brain regions of Alzheimer patients as well as the neurofibrillary tangles and senile plaques, sometimes in association with an increased aluminium content, such that the important question to be addressed is whether the brain iron homeostatic mechanisms are, or could be, perturbed by the presence of aluminium.

Iron Homeostasis and Aluminium Toxicity

Twelve brains of individuals with more than sixty-five years were studied. These samples were submitted to three techniques, with the objective to detect senile plaques which the major component was the β-amyloid: -β -amyloid immunohistochemistry; Glees technique; and haematoxilin-eosin technique. We detected significant differences between the number of senile plaques found in different techniques. β-amyloid immunohistochemistry was more efficient. This is very important because we can underdiagnosis Alzheimer's disease when the most adequate technique is not used. The statistical analysis showed no significant differences neither between the number of cortical plaques and the hipocampal plaques,nor between the number of plaques in both hemispheres. A literature review about neuropathological findings and β-amyloid importance was done.

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Alterações encontradas em cérebros de indivíduos acima dos 65 anos e sua correlação com demência de Alzheimer

Alzheimer's dementia is a severe form of dementia characterised by three neuropathological changes: amyloid plaques, neurofibrillary tangles and neurodegeneration. Several laboratories are involved in studies of the molecular mechanisms underlying development of Alzheimer's disease. As a result of recent research, the main component of amyloid plaques, the beta A4-peptide, is focused upon in hypotheses of the pathogenesis of the disease. The beta A4-peptide is produced by cleavage of the larger amyloid precursor protein (APP). During normal processing of APP, production of beta A4 is hindered and the peptide is therefore presumably a result of alternative cleavage mechanisms. Several factors may increase alternative processing of APP. One possibility is that conformational changes in APP, e.g. induced by mutations in the APP gene, may facilitate alternative cleavage of APP and thereby production of beta A4. This seems to be the case in certain families with familial Alzheimer's disease. Another possibility for increased beta A4 production is excessive expression of APP. This seems to be the case in persons with trisomy 21 who all have neuropathological signs of Alzheimer's disease after the age of 40 years. The gene for APP is localised to the human chromosome 21 and these persons have 1.5 times the normal expression of APP. Furthermore, excessive APP-expression may be induced by an acute phase response in the brain. In vitro studies and neuropathological examinations indicate that alpha 2-macroglobulin in neurons may be induced by cytokines. The protease inhibitor activity of this protein may prevent normal cleavage of APP, thereby resulting in increased alternative cleavage and deposition of beta A4.(ABSTRACT TRUNCATED AT 250 WORDS)

Blom N

Papers

[Alzheimer's dementia and amyloid precursor-protein].