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Free Radic Biol Med ; 130: 458-470, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30448512

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the brain. It cannot be cured currently, and those suffering from AD place a great burden on their caregivers and society. AD is characterized by high levels of iron ions in the brain, which catalyze radicals that damage the neurons. Knowing that the Aß42 peptide precipitates iron by binding iron ions at amino acid residues D1, E3, H11, H13, and H14, we synthesized a 5-repeat (HAYED) sequence peptide. By treating iron-stressed SH-SY5Y cells with it and injecting it into the cerebrospinal fluid (CSF) of naturally senescence Kunming mouse, which displaying AD-similar symptoms such as learning and memory dysfunction, neuron degeneration and high level of iron in brain, we found that HAYED (5) decreased the iron and radical levels in the cell culture medium and in the CSF. Specially, the synthesized peptide prevented cell and brain damage. Furthermore, functional magnetic resonance imaging (fMRI), Morris water maze and passive avoidance tests demonstrated that the peptide ameliorated brain blood-oxygen metabolism and slowed cognitive loss in the experimental senescence mice, and clinical and blood tests showed that HAYED (5) was innoxious to the kidney, the liver and blood and offset the AD-associated inflammation and anemia.


Assuntos
Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/farmacologia , Envelhecimento/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ferro/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Doenças Neurodegenerativas/patologia , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/química , Fragmentos de Peptídeos/síntese química
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