Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Drug Deliv Transl Res ; 9(1): 394-403, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30136122

RESUMO

Alzheimer's disease (AD) is currently incurable and places a large burden on the caregivers of AD patients. In the AD brain, iron is abundant, catalyzing free radicals and impairing neurons. The blood-brain barrier hampers antidementia drug delivery via circulation to the brain, which limits the therapeutic effects of drugs. Here, according to the method described by Gobinda, we synthesized a 16 lysine (K) residue-linked low-density lipoprotein receptor-related protein (LRP)-binding amino acid segment of apolipoprotein E (K16APoE). By mixing this protein with our designed therapeutic peptide HAYED, we successfully transported HAYED into an AD model mouse brain, and the peptide scavenged excess iron and radicals and decreased the necrosis of neurons, thus easing AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Apolipoproteínas E/química , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/química , Peptídeos/administração & dosagem , Animais , Apolipoproteínas E/metabolismo , Transporte Biológico , Barreira Hematoencefálica/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Ferro/química , Camundongos , Peptídeos/química
2.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA