Resumo

LEAL, María Celeste; FERNANDEZ GAMBA, Agata; MORELLI, Laura  e  CASTANO, Eduardo M.. Cerebral proteolysis of amyloid-ß peptide: Relevance of insulin-degrading enzyme in Alzheimer's disease. Medicina (B. Aires) [online]. 2009, vol.69, n.4, pp.466-472. ISSN 0025-7680.

The global increase in life expectancy turns Alzheimer's disease (AD) into a growing problem. One of the distinctive features of AD is the excessive accumulation of amyloid-ß (Aß) peptide in the brain. In recent years, a concept that has gained strength is that degradation of Aß by proteases in situ is an important mechanism that prevents cerebral peptide accumulation. Biochemical and genetic data have shown that insulin-degrading enzyme (IDE) participates in Aß and insulin homeostasis. IDE expression and activity are significantly decreased in AD brains compared to age-matched controls. Also, IDE is deposited with Aß in senile plaques and blood vessels, indicating a gross conformational change as a consequence of diverse post-translational mechanisms. These alterations in IDE distribution and activity may result in insufficient degradation of Aß and insulin, promoting the formation of Aß oligomers and hormone resistance. Both processes might play a fundamental part in neurodegeneration. The study of the clearance mechanisms of cerebral Aß will not only aid in the understanding AD pathogenesis but will also allow a better interpretation of ongoing clinical trials and the development of new therapeutic strategies.

Palavras-chave : Alzheimer's disease; Amyloid-ß peptide; Insulin degrading enzyme.

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